Native Niche Research Articles

Isolation, Identification, and Characterization of a Novel Bacteriocin Produced by Brevibacillus laterosporus DS-3 Against Methicillin-Resistant Staphylococcus aureus (MRSA)

Isolation and characterization of a bacteriocin from Brevibacillus laterosporus DS-3 and its ability in producing antibacterial activity were examined in this study. We isolated 48 bacterial strains from different native ecological niches. Sources included lake water, soil, air, and food. Among the isolates from the soil sample, morphological and biochemical tests identified Brev. laterosporus DS-3, which showed great potential for bacteriocin production. It was purified by ammonium sulfate precipitation, then applied in a Sephadex G-15 gel filtration column connected to a purification of AKTA Pure (USA) and reverse phase chromatography. MALDI-TOF mass spectrometry indicated that bacteriocin DS-3 has a low molecular weight of 1592.579 Da. LNTLETEEWFFK was identified as the sequence by mass spectrometry analysis in tandem liquid chromatography and MASCOT research. This bacteriocin inhibited Gram-positive and Gram-negative bacteria and was effective against Methicillin-resistant Staphylococcus aureus (MRSA). Brev. laterosporus DS-3 present in here is thermostable and tolerant to extreme pH. However, inactivation of its antibacterial activity was observed when treated with papain and trypsin but not pepsin, proteinase K, and catalase.

Niche expansion of the invasive plant species Ageratina adenophora despite evolutionary constraints

AbstractAimEcological inferences drawn from studies on niche dynamics of invasive species are often limited due to difficulties in disentangling evolutionary adaptations of the fundamental niche from demographic and interspecific processes shaping the realized niche. We used Ageratina adenophora, an invasive plant with restricted evolutionary potential to investigate shifts in the realized climatic niche independent of potential evolutionary adaptations.LocationNative Mexican range; exotic ranges in Asia, the USA, the Canary Islands and Australia.TaxonInvasive Asteraceae A. adenophora (Spreng.) R.M.King & H.Rob. Commonly known as Crofton weed.MethodsWe compiled a robust occurrence dataset of A. adenophora for its native Mexican range and four exotic ranges (Asia, USA, Canary Islands, and Australia) and quantified pairwise niche overlap (Schoener's D) and niche dynamic (stable, unfilling and expansion) indices between the native and exotic ranges in reduced climatic space using smoothed occurrence densities. Niche shift was statistically tested using niche equivalency tests.ResultsThe value of niche overlap (Schoener's D) differed considerably, ranging from relatively high between Mexico and Asia to low between Mexico and Australia. The niche dynamic indices indicated highest level of niche stability in Asia while highest degree of unstable niche was detected in Australia due to both niche expansion and unfilling. The niche similarity tests indicated that the native niche is more similar to the exotic niche than any randomly sampled niche from the exotic range. However, the niche equivalency tests showed evidence of niche differentiation as the observed niche overlap was lower than expected by chance for all pairwise comparisons. Jointly these tests indicate that despite the similarity, the native niche is not perfectly identical to any of the exotic niches.Main conclusionsThe current study has direct implications for understanding range expansion of invasive species even in the absence of evolutionary adaptation. Our study indicates that invasive species can occupy different, non‐consistent realized climatic niches in different parts of the world, thus limiting the transferability of species distribution models and corresponding risk assessments or future projections.

Engineered Biomimetic Neural Stem Cell Niche.

Neural stem cells (NSCs) have the potential to proliferate and differentiate into functional neurons, heightening their potential use for therapeutic applications. This review explores bioengineered systems which recapitulate NSC niche cell-cell and cell-matrix interactions. Delivery of NSCs to the cytotoxic injured brain is limited by low cell survival rates post-transplantation and poor maintenance of native niche bioactive components. The use of biomaterial platforms can mimic in vivo the environment of the two germinal areas of the adult brain in which NSCs thrive. An environmental mimic that includes extracellular proteins and moieties, along with appropriate biomechanical cues has recently demonstrated promising results in enhancing neurogenesis, aiding the production of a bioengineered niche. Biocomposition, biomechanics, and biostructure can be manipulated through engineered platforms to re-create the biofunctionality of an NSC niche. Upon transplantation and delivery with biomimetic scaffolds, NSCs show potential to promote functional recovery and rebuild neural circuitry post neurological trauma.

Stem Cells: Muscle Cells Enwrap Escaped Germline Stem Cells in C. elegans

Interactions between the distal tip cell and germline stem cells maintain a proliferative pool of mitotic cells in the Caenorhabditis elegans gonad. A new study shows that escaped germline stem cells induce nearby muscle cells to reach out and wrap around them, forming an ectopic niche similar to the native gonadal germ cell niche.

Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro.

Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease - including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve bio-chemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs.

Rapid adaptation to cold in the invasive cane toad Rhinella marina.

Understanding rapid adaptation to novel environments is essential as we face increasing climatic change. Invasive species are an ideal system for studying adaptation as they are typically introduced to novel environments where they must adapt if they are to persist. We used the invasive cane toad, Rhinella marina, to investigate the contribution of plasticity and evolution to rapid adaptation in a novel environment. Rhinella marina is a neotropical toad that has invaded areas with climates outside of its native environmental niche. The goal of this research was to understand how cane toads persist in northern Florida, the coldest region of their combined natural and invasive range, and originally thought to be beyond their thermal breadth. We measured Critical thermal minima in cane toads from the original, warm introduction location (Miami), and their northern range edge (Tampa) to determine whether northern toads were more cold-tolerant, and to examine the contribution of adaptive plasticity and evolution to any changes in tolerance. Our results show that following acclimation to cold temperatures, southern toads are less tolerant of cold than northern toads. This persistent population difference implies selection for cold-tolerance in northern populations. Differences in individual responses indicate that plasticity is also involved in this response. Our findings have implications for conservation because predatory cane toad invasions threaten local faunas, especially native amphibians. Characterizing specific adaptive mechanisms that allow R. marina to expand its range will identify evolutionary processes that shape a highly successful invasive species.

Rationally Designed 3D Hydrogels Model Invasive Lung Diseases Enabling High-Content Drug Screening.

Cell behavior is highly dependent upon microenvironment. Thus, to identify drugs targeting metastatic cancer, screens need to be performed in tissue mimetic substrates that allow cell invasion and matrix remodeling. A novel biomimetic 3D hydrogel platform that enables quantitative analysis of cell invasion and viability at the individual cell level is developed using automated data acquisition methods with an invasive lung disease (lymphangioleiomyomatosis, LAM) characterized by hyperactive mammalian target of rapamycin complex 1 (mTORC1) signaling as a model. To test the lung-mimetic hydrogel platform, a kinase inhibitor screen is performed using tuberous sclerosis complex 2 (TSC2) hypomorphic cells, identifying Cdk2 inhibition as a putative LAM therapeutic. The 3D hydrogels mimic the native niche, enable multiple modes of invasion, and delineate phenotypic differences between healthy and diseased cells, all of which are critical to effective drug screens of highly invasive diseases including lung cancer.

Naturalized distributions show that climatic disequilibrium is structured by niche size in pines (PinusL.)

AbstractAimThe assumption that the native distributions of species are in equilibrium with climate has been shown to be frequently violated, despite its centrality to many niche model applications. We currently lack a framework that predicts these violations. Here, we examine whether variation in climatic disequilibrium is structured by properties of species’ native distributions and climatic niches.LocationGlobal.MethodsWe built climatic niche models for 106 pine (PinusL.) species, including 25 that have naturalized outside their native range. We measured the extent of climate space occupied exclusively by naturalized populations and considered what fraction of this space was available within the native continent and near the native range. We examined the consequences of disequilibrium for estimates of potential range filling and sister species niche conservatism.ResultsMost species (23 of 25) have naturalized in climate conditions outside the native niche, leading to increases in the total known suitable climate space. Increases in niche size were negatively related to native niche size. Increases were often large; one species expanded its niche by almost 10% of the global climate space. These increases were associated primarily with cooler, wetter and less seasonal climates. Increases in known niche size lowered potential range filling estimates within species’ native continent and ecoregion. Naturalized data did not strengthen support for niche conservatism among sister species.Main conclusionsAmong pines, climatic disequilibrium is the norm and not the exception. The magnitude of this disequilibrium can be vast, such that the native range greatly under‐represents the true climatic tolerances of some species. Fortunately, this disequilibrium can be predicted largely by the size of a species’ native niche. Accounting for this disequilibrium can improve our ability to characterize ecological phenomena, including potential range filling. This is an essential step towards improving the conservation value of ecological niche models.

Characterization of the Kinetics and Mechanism of Degradation of Human Mesenchymal Stem Cell-Laden Poly(ethylene glycol) Hydrogels.

Human mesenchymal stem cells (hMSCs) are motile cells that migrate from their native niche to wounded sites where they regulate inflammation during healing. New materials are being developed as hMSC delivery platforms to enhance wound healing. To act as an effective wound healing material, the hydrogel must degrade at the same rate as tissue regeneration, while maintaining a high cell viability. This work determines the kinetics and mechanism of cell-mediated degradation in hMSC-laden poly(ethylene glycol) (PEG) hydrogels. We use a well-established hydrogel scaffold that is composed of a backbone of four-arm star PEG functionalized with norbornene that is cross-linked with a matrix metalloproteinase (MMP) degradable peptide. This peptide sequence is cleaved by cell-secreted MMPs, which allow hMSCs to actively degrade the hydrogel during motility. Three mechanisms of degradation are characterized: hydrolytic, noncellular enzymatic and cell-mediated degradation. We use bulk rheology to characterize hydrogel material properties and quantify degradation throughout the entire reaction. Hydrolysis and noncellular enzymatic degradation are first characterized in hydrogels without hMSCs, and follow first-order and Michaelis-Menten kinetics, respectively. A high cell viability is measured in hMSC-laden hydrogels, even after shearing on the rheometer. After confirming hMSC viability, bulk rheology characterizes cell-mediated degradation. When comparing cell-mediated degradation to noncellular degradation mechanisms, cell-mediated degradation is dominated by enzymatic degradation. This indicates hydrogels with hMSCs are degraded primarily due to cell-secreted MMPs and very little network structure is lost due to hydrolysis. Modeling cell-mediated degradation provides an estimate of the initial concentration of MMPs secreted by hMSCs. By changing the concentration of hMSCs, we determine the initial MMP concentration increases with increasing hMSC concentration. This work characterizes the rate and mechanism of scaffold degradation, giving new insight into the design of these materials as implantable scaffolds.

Synthetic biodegradable alternatives to the use of the amniotic membrane for corneal regeneration: assessment of local and systemic toxicity in rabbits

AimThe aim of this study was to assess the local and systemic response to poly-lactic co-glycolic acid (PLGA) 50:50 membranes, developed as synthetic biodegradable alternatives to the use of human...

Decellularized human ovarian scaffold based on a sodium lauryl ester sulfate (SLES)-treated protocol, as a natural three-dimensional scaffold for construction of bioengineered ovaries

BackgroundThe increasing number of patients with ovarian insufficiency due to autoimmune disorders, genetic predisposition, or iatrogenic effects of treatment such as cancer therapies necessitates an urgent measure to find a safe and transplantable alternative ovary. A bioengineered ovary is one of the strategies on which the researchers have recently been working. An engineered ovary should be able to mimic the natural ovary aspects. Recent studies suggest that the decellularized organ-specific extracellular matrix-based scaffolds can serve as a native niche to bioengineering artificial organs. Therefore, we established a human decellularized ovarian scaffold based on a sodium lauryl ester sulfate (SLES)-treated process, as an optimized protocol.MethodsThe human ovary samples were decellularized with 1% SLES for 48 h followed by DNase I in PBS for 24 h, and then thoroughly rinsed in PBS to remove the cell remnants and chemical reagents. Efficient cell removal was confirmed by DNA content analysis, hematoxylin and eosin, and Hoechst staining. Preservation assessment of the extracellular matrix structures was performed by immunohistochemistry, histological staining, and scanning electron microscopy. An MTT test was done to assess the in vitro scaffold’s cytocompatibility, and finally in vivo studies were performed to evaluate the biocompatibility, bioactivity, and secretion functions of the ovarian grafts made of primary ovarian cells (POCs) on the decellularized scaffolds.ResultsEvidence provided by SEM, histochemical, and immunohistochemical analyses showed that the ovarian extracellular matrix was preserved after decellularization. Moreover, MTT test indicated the suitable cytocompatibility of the scaffolds. The in vivo assessment showed that the POCs kept their viability and bioactivity, and reconstructed the primordial or primary follicle-like structures within the scaffolds after transplantation. Immunostaining characterized somatic cells that were capable of expressing steroid hormone receptors; also, as a marker of granulosa cell, inhibin-α immunostaining demonstrated these cells within the grafts. Additionally, hormone assessment showed that serum estradiol and progesterone levels were significantly higher in ovariectomized rats with ovarian cells-seeded grafts than those with or without decellularized scaffold grafts.ConclusionsA human ovary-specific scaffold based on a SLES-decellularized protocol as a biomimicry of the natural ovarian niche can be an ideal scaffold used to reconstruct the ovary.

Membrane bioreactor to guide hepatic differentiation of human mesenchymal stem cells

The eminent role of the membrane technology in liver tissue engineering is already consolidated. Indeed, membranes with their geometry and intrinsic properties can modulate liver cell behavior and tissue organization. The development of a robust membrane-based engineered hepatic differentiation model has to satisfy a plethora of fundamental criteria with the aim to reproduce a biomimetic environment, which exposes the undifferentiated cells to their native niche. Within our membrane bioreactor, a large compendium of aspects for controlling key process variables are satisfied; thus providing an optimal setting in terms of fluid dynamic and membrane properties and offering optimal structural, topographical and trophic support to boost cell differentiation. The aim of this work is to develop a bioartificial membrane system with an ideal microenvironment for the promotion of stem cell differentiation towards a hepatic lineage. The homogeneous surrounding created by the continuous membrane perfusion enhanced the hepatic maturation in terms of gene expression, metabolic and synthetic functions. The work highlights the potential role of membrane systems as a useful investigational platform to study liver cell behavior in physiological and pathological conditions. In addition, it opens promising applications in the field of personalized medicine serving as controlled tool for disease modelling.

Estrogen matters in metastasis

Metastatic cancer cells meet several physical, biochemical and immunological barriers before colonizing a new territory. Cancerous cells turn invasive, mobile and eventually disengage from their native niche. This is followed by their intravasation, extravasation, survival, proliferation, and colonization into distant organs. Unlike well-confined tumors, which respond favorably to anti-cancer therapeutics, metastatic tumors are life-threatening and incurable. More than 90% of cancer-related mortality is caused by metastases, hence the emphasis is now on developing the strategies to block or reverse the process of metastasis. This has ensued intensive research with a focus on the mechanisms underlying metastasis. Substantial work carried out in this direction has led to the identification of specific enzymes, proteins, cytokines, chemokines, growth factors, exosomes, miRNA and lipids, etc. as the facilitators of metastasis. Metastatic cells are exposed to a diverse array of local and systemic signals. Among these, estrogens are of great relevance. Estrogens have been strongly linked to cancers, especially of breast and uterine origin. Recent data hint that estrogens, well recognized for their role in proliferation, may have a role in metastasis also. It is proposed that influence of estrogen on metastasis may be independent of its proliferation-inducing ability. Data are emerging to suggest that estrogens have potential to modulate various events of the metastatic cascade such as local invasion, intravasation, anoikis, immune evasion, extravasation, angiogenesis and metastatic colonization. This review summarizes some of the recent advances in our knowledge on the role of estrogens in the metastatic cascade of cancerous cells.

Exosomes from acellular Wharton\u2019s jelly of the human umbilical cord promotes skin wound healing

BackgroundCompromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. We recently reported that acellular gelatinous Wharton’s jelly of the human umbilical cord enhances skin wound healing in vitro and in vivo in a murine model; however, the key player in the jelly which enhances wound healing is still unknown.MethodsWe performed mass spectrometry on acellular gelatinous Wharton’s jelly to elucidate the chemical structures of the molecules. Using an ultracentrifugation protocol, we isolated exosomes and treated fibroblasts with these exosomes to assess their proliferation and migration. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or vehicle containing exosomes. Isolated exosomes were subjected to further mass spectrometry analysis to determine their cargo.ResultsSubjecting the acellular gelatinous Wharton’s jelly to proteomics approaches, we detected a large amount of proteins that are characteristic of exosomes. Here, we show that the exosomes isolated from the acellular gelatinous Wharton’s jelly enhance cell viability and cell migration in vitro and enhance skin wound healing in the punch biopsy wound model in mice. Mass spectrometry analysis revealed that exosomes of Wharton’s jelly umbilical cord contain a large amount of alpha-2-macroglobulin, a protein which mimics the effect of acellular gelatinous Wharton’s jelly exosomes on wound healing.ConclusionsExosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton’s jelly and the cargo protein alpha-2-macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.

Environmental context and differences between native and invasive observed niches of Batrachochytrium salamandrivorans affect invasion risk assessments in the Western Palaearctic

AbstractAimIdentifying hosts and regions susceptible to invasion by an emerged pathogen is vital to inform early risk assessments. We here show how differences between a pathogen's native and invasive observed niche and their underlying environments affect this process, using the recent emergence of Batrachochytrium salamandrivorans (Bsal) as a critical, empirical example.LocationPalaearctic.MethodsTo quantify observed niches, we first gathered occurrences from the native Asian and invasive European distribution of Bsal. Through ordination in PCA‐bound environmental space, we then applied overlap tests to compare native and invasive Bsal niches with those of 56 putative Western Palaearctic host species. At last, we ensembled bivariate niche models (ESMs) for each Bsal niche to assess how differences in observed niches influenced suitability predictions.ResultsThe observed invasive Bsal niche is a conservative, partially filled subset of its wider native niche. Pathogen–host overlap measured using the narrow invasive niche was nevertheless found to be significantly higher than that of the native niche, which is partly situated in subtropical conditions absent from the Western Palaearctic. ESMs created using the native niche predict high suitability for Bsal throughout Europe. Conversely, a more restricted range was predicted using the invasive niche, which coincides with the presence of oceanic climates in north‐western Europe and several Mediterranean mountain ranges.Main conclusionsUnequal relative availability of environments in native and invasive ranges may lead to underestimation of observed niche overlap between native pathogen populations and putative hosts in the invasive range. The existence of partially filled niches may add uncertainty to overlap measurements, and predictions of potential further spread. Results based on the invasive niche therefore provide a conservative estimate; yet demonstrate, in our case, that Bsal is already present in conditions shared by numerous host species. Further niche filling may accordingly increase risk of salamander diversity across the Western Palaearctic.

Fractionated human adipose tissue as a native biomaterial for the generation of a bone organ by endochondral ossification

Many steps are required to generate bone through endochondral ossification with adipose mesenchymal stromal cells (ASC), from cell isolation to in vitro monolayer expansion, seeding into scaffolds, cartilaginous differentiation and in vivo remodeling. Moreover, monolayer expansion and passaging of ASC strongly decreases their differentiation potential. Here, we propose that adipose tissue itself can be used as scaffold for ASC expansion and endochondral ossification. Human liposuctions were fractionated and cultured for 3 weeks with proliferative medium in suspension. The resulting constructs, named Adiscaf, were compared to constructs generated with a previously developed, control approach, i.e. collagen sponges seeded with monolayer-expanded ASC. After 4 weeks of chondrogenic differentiation, Adiscaf contained cartilage tissue, characterized by glycosaminoglycans and collagen type II. After 2 additional weeks of hypertrophic differentiation, Adiscaf showed upregulation of hypertrophic markers at the gene expression and protein levels. After 8 weeks of in vivo implantation, Adiscaf resulted in ectopic bone tissue formation, including bone marrow elements. Adiscaf showed superior in vitro differentiation and in vivo performance as compared to the control paradigm involving isolation and monolayer expansion of ASC. This new paradigm exploits the physiological niche of adipose tissue and strongly suggests a higher functionality of cells inside adipose tissue after in vitro expansion. This study demonstrates that adult human adipose tissue used as a native construct can generate a bone organ by endochondral ossification. The concept could be exploited for the generation of osteogenic grafts for bone repair. Statement of SignificanceIn this study we used adult human adipose tissue as scaffolding materials (called Adiscaf) to generate a bone organ by endochondral ossification. Adiscaf concept is based on the culture of adipose tissue cells inside their native microenvironment for the generation of osteogenic grafts for bone repair. This simplified approach overcomes several limitations linked to the current techniques in bone tissue engineering, such as isolation of cells and inadequate properties of the biomaterials used as scaffolds. In addition, the present paradigm proposes to exploit physiological niches in order to better maintain the functionality of cells during their in vitro expansion. This project not only has a scientific impact by evaluating the impact of native physiological niches on the functionality and chondrogenic differentiation of mesenchymal progenitors but also a clinical impact to generate osteogenic grafts and/or osteoinductive materials for bone regeneration and repair.

Abstract 2433: The hypoxic tumor microenvironment in vivo selects the tumor cells with cancer stem cell characteristics and increased resistance against genotoxic stresses

Abstract Tumor hypoxia has been established as an independent prognostic factor associated with poor patient survival and resistance to conventional therapies. Emerging evidence suggests that hypoxia has the potential to maintain or enhance the stem cell phenotype and confers chemo- or radio-resistance to tumor cells. However, it remains to be determined whether cell fate and acquisition of therapy resistance is regulated in vivo by the hypoxic tumor microenvironment (TME). In this study, we have developed a hypoxia-sensing human breast cancer cell xenograft model using the hypoxia-response element (HRE)-driven enhanced green fluorescence protein (EGFP) as a hypoxia reporter. We have found that the hypoxic tumor cells isolated from xenografts contain increased subpopulations of tumor cells showing the cancer stem cell (CSC) characteristics. Upon re-implantation, the CSC characteristics of the hypoxic tumor cells continue to be further enriched during in vivo growth, whereas secondary xenografts derived from the non-hypoxic tumor cells remain similar to the primary xenografts. Consistent with this finding, the phenotypes exhibited by the hypoxic tumor cells are stably different from those of the non-hypoxic tumor cells isolated from the same tumor mass even when they are maintained under the same ambient culture conditions. Mechanistically, we find that the PI3K/AKT pathway is strongly potentiated in the hypoxic tumor cells and is required to maintain the CSC phenotype. Cell fate differences between hypoxic and non-hypoxic tumor cells are found only in tumor cells isolated from the hypoxic TME in vivo, and are not seen in tumor cells treated by hypoxia in vitro alone. In addition, we have found that naturally hypoxic tumor cells in a breast cancer xenograft model are moderately radio- and chemo-resistant compared to their neighboring non-hypoxic tumor cells in the same tumor. These naturally hypoxic tumor cells are proficient at repairing DNA damages and resist apoptosis induced by genotoxic stresses. The ex vivo hypoxic tumor cells are capable of proficient activation of the DNA damage-sensing pathways, especially the ATM pathway. These previously unrecognized observations suggest that the hypoxic TME may promote malignant progression by coordinating induction, selection and preferential maintenance of the CSC phenotype in tumor cells. This presentation will review our results which strongly suggest that the hypoxic TME may induce adaptive responses, either by clonal evolution or selection, such that hypoxic tumor cells in vivo acquire new functional traits that confer resistance to genotoxic stresses and enhance survival. It can be postulated that previously hypoxic tumor cells may continue to exhibit their aggressive phenotypes long after they have migrated into non-hypoxic regions or after their native niche become normoxic. Citation Format: Hoon Kim, Qun Lin, Zhong Yun. The hypoxic tumor microenvironment in vivo selects the tumor cells with cancer stem cell characteristics and increased resistance against genotoxic stresses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2433.

The potential invasiveness of an aquatic macrophyte reflects founder effects from native niche

Biological invasions are important drivers of biodiversity loss. Hence, predicting invasion risks considering the invasion history of a species might help drive meaningful conservation strategies. We investigated the niche dynamics occurring during the invasion of Hydrilla verticillata in North and South America. Because of founder effects, we hypothesised that occupied invaded area niches across North and South American are a subset of the occupied niche in the native range. Moreover, according to the invasion history, we expected that the South American niche is more similar to the North American one than the native niche. We built ecological niche models to predict the potential distribution of hydrilla from native and invaded occurrence records, as well as analysing niche overlap, equivalency, and similarity between the native and two invaded areas. Although the models predicted spatially congruent suitable sites, the ones based on native occurrence records predicted larger geographical ranges for hydrilla across South America than those based on the records of its North American invasions. The environmental conditions the species occupied in both invaded areas are modestly overlapped with the native area (Schoener’s D < 0.6), with native and South American niches showing the highest overlap and significant equivalency. Contrary to our prediction, the invaded North and South American niches presented the smallest niche overlap. Our findings suggest that founder effects triggered deep shifts in hydrilla’s occupation abilities across invaded areas, but do not support successive invasion events. Hydrilla’s Grinnellian niche was maintained throughout the invaded areas, and its potential invasion across South America is massive, regardless of its origin.

Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence

Physical properties of modifiable hydrogels can be tuned to direct stem cell differentiation in a role akin to that played by the extracellular matrix in native stem cell niches. However, stem cells do not respond to matrix cues in isolation, but rather integrate soluble and non-soluble signals to balance quiescence, self-renewal and differentiation. Here, we encapsulated single cell suspensions of human mesenchymal stem cells (hMSC) in hyaluronic acid-based hydrogels at high and low densities to unravel the contributions of matrix- and non-matrix-mediated cues in directing stem cell response. We show that in high-density (HD) cultures, hMSC do not rely on hydrogel cues to guide their fate. Instead, they take on characteristics of quiescent cells and secrete a glycoprotein-rich pericellular matrix (PCM) in response to signaling from neighboring cells. Preventing quiescence precluded the formation of a glycoprotein-rich PCM and forced HD cultures to differentiate in response to hydrogel composition. Our observations may have important implications for tissue engineering as neighboring cells may act counter to matrix cues provided by scaffolds. Moreover, as stem cells are most regenerative if activated from a quiescent state, our results suggest that ex vivo native-like niches that incorporate signaling from neighboring cells may enable the production of clinically relevant, highly regenerative cells.

Niche conservatism of Aedes albopictus and Aedes aegypti - two mosquito species with different invasion histories

Biological invasions have been associated with niche changes; however, their occurrence is still debated. We assess whether climatic niches between native and non-native ranges have changed during the invasion process using two globally spread mosquitoes as model species, Aedes albopictus and Aedes aegypti. Considering the different time spans since their invasions (>300 vs. 30–40 years), niche changes were expected to be more likely for Ae. aegypti than for Ae. albopictus. We used temperature and precipitation variables as descriptors for the realized climatic niches and different niche metrics to detect niche dynamics in the native and non-native ranges. High niche stability, therefore, no niche expansion but niche conservatism was revealed for both species. High niche unfilling for Ae. albopictus indicates a great potential for further expansion. Highest niche occupancies in non-native ranges occurred either under more temperate (North America, Europe) or tropical conditions (South America, Africa). Aedes aegypti has been able to fill its native climatic niche in the non-native ranges, with very low unfilling. Our results challenge the assumption of rapid evolutionary change of climatic niches as a requirement for global invasions but support the use of native range-based niche models to project future invasion risk on a large scale.