Native Niche Research Articles

Planctomycetes as Host-Associated Bacteria: A Perspective That Holds Promise for Their Future Isolations, by Mimicking Their Native Environmental Niches in Clinical Microbiology Laboratories.

Traditionally recognized as environmental bacteria, Planctomycetes have just been linked recently to human pathology as opportunistic pathogens, arousing a great interest for clinical microbiologists. However, the lack of appropriate culture media limits our future investigations as no Planctomycetes have ever been isolated from patients’ specimens despite several attempts. Several Planctomycetes have no cultivable members and are only recognized by 16S rRNA gene sequence detection and analysis. The cultured representatives are slow-growing fastidious bacteria and mostly difficult to culture on synthetic media. Accordingly, the provision of environmental and nutritional conditions like those existing in the natural habitat where yet uncultured/refractory bacteria can be detected might be an option for their potential isolation. Hence, we systematically reviewed the various natural habitats of Planctomycetes, to review their nutritional requirements, the physicochemical characteristics of their natural ecological niches, current methods of cultivation of the Planctomycetes and gaps, from a perspective of collecting data in order to optimize conditions and the protocols of cultivation of these fastidious bacteria. Planctomycetes are widespread in freshwater, seawater, and terrestrial environments, essentially associated to particles or organisms like macroalgae, marine sponges, and lichens, depending on the species and metabolizable polysaccharides by their sulfatases. Most Planctomycetes grow in nutrient-poor oligotrophic environments with pH ranging from 3.4 to 11, but a few strains can also grow in quite nutrient rich media like M600/M14. Also, a seasonality variation of abundance is observed, and bloom occurs in summer-early autumn, correlating with the strong growth of algae in the marine environments. Most Planctomycetes are mesophilic, but with a few Planctomycetes being thermophilic (50°C to 60°C). Commonly added nutrients are N-acetyl-glucosamine, yeast-extracts, peptone, and some oligo and macro-elements. A biphasic host-associated extract (macroalgae, sponge extract) conjugated with a diluted basal medium should provide favorable results for the success of isolation in pure culture.

Organ-specific ECM arrays for investigating cell-ECM interactions during stem cell differentiation

Pluripotent stem cells are promising source of cells for tissue engineering, regenerative medicine and drug discovery applications. The process of stem cell differentiation is regulated by multi-parametric cues from the surrounding microenvironment, one of the critical one being cell interaction with extracellular matrix (ECM). The ECM is a complex tissue-specific structure which is an important physiological regulator of stem cell function and fate. Recapitulating this native ECM microenvironment niche is best facilitated by decellularized tissue/organ derived ECM, which can faithfully reproduce the physiological environment with high fidelity to in vivo condition and promote tissue-specific cellular development and maturation. Recognizing the need for organ specific ECM in a 3D culture environment in driving phenotypic differentiation and maturation of hPSCs, we fabricated an ECM array platform using native-mimicry ECM from decellularized organs (namely pancreas, liver and heart), which allows cell-ECM interactions in both 2D and 3D configuration. The ECM array was integrated with rapid quantitative imaging for a systematic investigation of matrix protein profiles and sensitive measurement of cell-ECM interaction during hPSC differentiation. We tested our platform by elucidating the role of the three different organ-specific ECM in supporting induced pancreatic differentiation of hPSCs. While the focus of this report is on pancreatic differentiation, the developed platform is versatile to be applied to characterize any lineage specific differentiation.

In Vivo Pre-Instructed HSCs Robustly Execute Asymmetric Cell Divisions In Vitro.

Hematopoietic stem cells (HSCs) are responsible for life-long production of all mature blood cells. Under homeostasis, HSCs in their native bone marrow niches are believed to undergo asymmetric cell divisions (ACDs), with one daughter cell maintaining HSC identity and the other committing to differentiate into various mature blood cell types. Due to the lack of key niche signals, in vitro HSCs differentiate rapidly, making it challenging to capture and study ACD. To overcome this bottleneck, in this study, we used interferon alpha (IFNα) treatment to ”pre-instruct” HSC fate directly in their native niche, and then systematically studied the fate of dividing HSCs in vitro at the single cell level via time-lapse analysis, as well as multigene and protein expression analysis. Triggering HSCs’ exit from dormancy via IFNα was found to significantly increase the frequency of asynchronous divisions in paired daughter cells (PDCs). Using single-cell gene expression analyses, we identified 12 asymmetrically expressed genes in PDCs. Subsequent immunocytochemistry analysis showed that at least three of the candidates, i.e., Glut1, JAM3 and HK2, were asymmetrically distributed in PDCs. Functional validation of these observations by colony formation assays highlighted the implication of asymmetric distribution of these markers as hallmarks of HSCs, for example, to reliably discriminate committed and self-renewing daughter cells in dividing HSCs. Our data provided evidence for the importance of in vivo instructions in guiding HSC fate, especially ACD, and shed light on putative molecular players involved in this process. Understanding the mechanisms of cell fate decision making should enable the development of improved HSC expansion protocols for therapeutic applications.

Ecological niche modeling (ENM) of Leptoglossus clypealis a new potential global invader: following in the footsteps of Leptoglossus occidentalis?

The introduction of alien species is one of the main problems in conservation. Many successful invaders cause severe economic and ecological damage. Such is the case of Leptoglossus occidentalis, a phytophagous true bug native to North America, which has become a pest in Europe, Asia, Africa and South America. Within the genus, another species whose distributional range is expanding toward the east of North America is Leptoglossus clypealis. As climate determines the successful establishment of insects, the identification of climatically suitable areas for invasive species based on ecological niche models (ENMs) offers an excellent opportunity for preventing invasions. In this study, ENMs were built for both species and their native climatic niches were compared. Their niche breath was also measured. The climatic niches of both species are identical and the niche breadth of L. clypealis is broader than that of L. occidentalis. In view of the great ecological resemblance between these two species, we believe that L. clypealis could became a major pest thus it should be carefully monitored. The results of the present worldwide ENMs showed numerous regions with suitable conditions for the establishment of both species. The future ENMs exhibited a retraction in the suitable areas in North America, Europe and Asia.

Bioactive and Topographically-Modified Electrospun Membranes for the Creation of New Bone Regeneration Models

Bone injuries that arise from trauma, cancer treatment, or infection are a major and growing global challenge. An increasingly ageing population plays a key role in this, since a growing number of fractures are due to diseases such as osteoporosis, which place a burden on healthcare systems. Current reparative strategies do not sufficiently consider cell-substrate interactions that are found in healthy tissues; therefore, the need for more complex models is clear. The creation of in vitro defined 3D microenvironments is an emerging topographically-orientated approach that provides opportunities to apply knowledge of cell migration and differentiation mechanisms to the creation of new cell substrates. Moreover, introducing biofunctional agents within in vitro models for bone regeneration has allowed, to a certain degree, the control of cell fate towards osteogenic pathways. In this research, we applied three methods for functionalizing spatially-confined electrospun artificial microenvironments that presented relevant components of the native bone stem cell niche. The biological and osteogenic behaviors of mesenchymal stromal cells (MSCs) were investigated on electrospun micro-fabricated scaffolds functionalized with extracellular matrix (ECM) proteins (collagen I), glycosaminoglycans (heparin), and ceramic-based materials (bioglass). Collagen, heparin, and bioglass (BG) were successfully included in the models without modifying the fibrous structures offered by the polycaprolactone (PCL) scaffolds. Mesenchymal stromal cells (MSCs) were successfully seeded in all the biofunctional scaffolds and they showed an increase in alkaline phosphatase production when exposed to PCL/BG composites. This research demonstrates the feasibility of manufacturing smart and hierarchical artificial microenvironments for studying stem cell behavior and ultimately the potential of incorporating these artificial microenvironments into multifunctional membranes for bone tissue regeneration

Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function.

Aging is associated with reduced fitness and increased myeloid bias of the hematopoietic stem cell (HSC) compartment, causing increased risk of immune compromise, anemia, and malignancy. We show that mitochondrial membrane potential (MMP) can be used to prospectively isolate chronologically old HSCs with transcriptional features and functional attributes characteristic of young HSCs, including a high rate of transcription and balanced lineage-affiliated programs. Strikingly, MMP is a stronger determinant of the quantitative and qualitative transcriptional state of HSCs than chronological age, and transcriptional consequences of manipulation of MMP in HSCs within their native niche suggest a causal relationship. Accordingly, we show that pharmacological enhancement of MMP in old HSCs invivo increases engraftment potential upon transplantation and reverses myeloid-biased peripheral blood output at steady state. Our results demonstrate that MMP is a source of heterogeneity in old HSCs, and its pharmacological manipulation can alter transcriptional programs with beneficial consequences for function.

Basic Science of Resident Stem Cells

A natural reservoir of stem/progenitor cells exists in most tissues of the musculoskeletal system including cartilage, meniscus, ligament, tendon, bone, muscle, and the synovial membrane. These resident stem cells are important during development, but also for replacement of tissue cells during aging and in injury. Most stem cells exist in a resting, quiescent state and in a tissue –specific specialized microenvironment known as a stem cell niche. Resident stem cells are activated during injury to facilitate endogenous repair but the natural response is often insufficient for functional tissue repair. Autologous approaches that leverage resident stem cells in regenerative medicine could enhance the facilitated recruitment of stem cells to the site of injury or the retention of stem cells in their native niche during autologous transplantation. Evolving knowledge about resident stem cells and the stem cell niche will lead to a better understanding about musculoskeletal injury and regenerative medicine approaches to tissue repair.

Smaller climatic niche shifts in invasive than non-invasive alien ant species

The globalization of trade and human movement has resulted in the accidental dispersal of thousands of alien species worldwide at an unprecedented scale. Some of these species are considered invasive because of their extensive spatial spread or negative impacts on native biodiversity. Explaining which alien species become invasive is a major challenge of invasion biology, and it is often assumed that invasiveness is linked to a greater ability to establish in novel climates. To test whether invasive species have expanded more into novel climates than non-invasive alien species, we quantified niche shifts of 82 ant species. Surprisingly, invasive species showed smaller niche shifts than non-invasive alien species. Independent of their invasiveness, the species with the smallest native niches and range sizes, experienced the greatest niche shifts. Overall, our results challenge the assumption that invasive species are particularly good pioneers of novel climates.

Nesting and fate of transplanted stem cells in hypoxic/ischemic injured tissues: The role of HIF1α/sirtuins and downstream molecular interactions.

The nesting mechanisms and programming for the fate of implanted stem cells in the damaged tissue have been critical issues in designing and achieving cell therapies. The fracture site can induce senescence or apoptosis based on the surrounding harsh conditions, hypoxia, and oxidative stress (OS). Respiration deficiency, disruption in energy metabolism, and consequently OS induction change the biophysical, biochemical, and cellular components of the native tissue. Additionally, the homeostatic molecular players and cell signaling might be changed. Despite all aforementioned issues, in the native stem cell niche, physiological hypoxia is not toxic; rather, it is vitally required for homing, self-renewal, and differentiation. Hence, the key macromolecular players involved in the support of stem cell survival and re-adaptation to a new dysfunctional niche must be understood for managing the cell therapy outcome. Hypoxia-inducible factor 1-alpha is the master transcriptional regulator, involved in the cell response to hypoxia and the adaptation of stem cells to a new niche. This protein is regulated by interaction with sirtuins. Sirtuins are highly conserved NAD+-dependent enzymes that monitor the cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals to modulate the homing and fate of stem cells. Herein, new insights into the nesting of stem cells in hypoxic-ischemic injured tissues were provided and their programming in a new dysfunctional niche along with the involved complex macromolecular players were critically discussed.

Regeneration enhanced in critical-sized bone defects using bone-specific extracellular matrix protein.

Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue-specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM-MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence-activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM-MSC response to bone marrow specific ECM (BM-ECM). BM-ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM-ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical-sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM-ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM-ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM-ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm4 with BM-ECM supplementation compared to 48 ± 0.2 mm4 in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM-ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.

Most invasive species largely conserve their climatic niche

The ecological niche is a key concept for elucidating patterns of species distributions and developing strategies for conserving biodiversity. However, recent times are seeing a widespread debate whether species niches are conserved across space and time (niche conservatism hypothesis). Biological invasions represent a unique opportunity to test this hypothesis in a short time frame at the global scale. We synthesized empirical findings for 434 invasive species from 86 studies to assess whether invasive species conserve their climatic niche between native and introduced ranges. Although the niche conservatism hypothesis was rejected in most studies, highly contrasting conclusions for the same species between and within studies suggest that the dichotomous conclusions of these studies were sensitive to techniques, assessment criteria, or author preferences. We performed a consistent quantitative analysis of the dynamics between native and introduced climatic niches reported by previous studies. Our results show there is very limited niche expansion between native and introduced ranges, and introduced niches occupy a position similar to native niches in the environmental space. These findings support the niche conservatism hypothesis overall. In particular, introduced niches were narrower for terrestrial animals, species introduced more recently, or species with more native occurrences. Niche similarity was lower for aquatic species, species introduced only intentionally or more recently, or species with fewer introduced occurrences. Climatic niche conservatism for invasive species not only increases our confidence in transferring ecological niche models to new ranges but also supports the use of niche models for forecasting species responses to changing climates.

Abstract LB-360: Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells

Abstract Immune signaling within a metastatic niche drives recruitment and colonization, and the subsequent tumor cell fate within the niche. We employed a biomaterial scaffold as a synthetic metastatic niche to dissect the signals driving the responses within the niche relative to the native metastatic niche, which was the lung in these models. For both the natural and the synthetic niche, Gr-1+ cells secreting S100A8/A9 were the major factors contributing to tumor cell recruitment. Interestingly, upon recruitment, tumor cells in the synthetic niche were observed to undergo senescence and were cleared whereas cells within the native niche accumulated and ultimately proliferated to form macrometastases. The synthetic niche has underlying inflammation due to the foreign body responses (FBR) consisting of N1-polarized Gr1+ myeloid cells, M1-polarizedmacrophage, mature dendritic cells and highly cytotoxic CTLs and NK cells, which were not observed in the lung. Furthermore, we found two proteins (osteopontin and decorin) that are associated with developing FBR greatly improve the cytotoxicity of CTLs and NK cells in the lung from stage 3 breast cancers by increasing their production of Perforin/Granzyme, Fas/TRAIL and IFNr/TNFa. Our results highlight the potential of FBR-associated biomolecules to be used as immune-editing anticancer drugs and also inspire the development of therapeutic implants to actively catch and eradicate metastatic cells. Citation Format: Jing Wang, Matthew Hall, Grace Bushnell, Joseph Decker, Sophia Orbach, Ravi Raghani, Yining Zhang, Aaron Morris, Jeffery Ma, Pridvi Kandagatla, Jacqueline Jeruss, Lonnie Shea. Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-360.

A global assessment of human influence on niche shifts and risk predictions of bird invasions

AbstractAimEstimating the strength of niche conservatism is key for predictions of invasion risk. Most studies consider only the climatic niche, but other factors, such as human disturbance, also shape niches. Whether occupation of human habitats in the alien range depends on the native tolerances of species remains unexplored. We assessed niche conservatism in climatic and human spaces for bird species showing different responses to humans in native ranges and evaluated whether considering anthropogenic niche variables affects invasion predictions.LocationGlobal.Time periodFrom 500 CE to the present day.Major taxon studiedBirds.MethodsWe assessed niche conservatism by comparing the native and alien distributions of 150 bird species. We differentiated “niche expansions” into environments new to the species and “niche unfilling”, whereby a species fills its native niche only in part. Global predictions of alien bird distribution were generated using species distribution models (SDMs).ResultsClimatic niche similarity was higher than random expectation in 56% of species, and human disturbance niche similarity in 43%. Only 34 and 15% of species had >10% of their alien distribution in climates or human conditions, respectively, different from those of native ranges. Climatic niche expansions mostly involved colonization of colder and less seasonal climates. Human niche expansions involved colonization of more disturbed environments by species not responding positively to human influence in native ranges. Climatic and human niche unfilling was more common than expansions and was lower for species introduced earlier and those responding positively to human influence. Models including human variables do equally well for all species.Main conclusionsAlien birds tend to invade areas with similar climatic and human conditions to their native range, but niche unfilling and expansions occur and relate to species native tolerances to human‐modified habitats and first introduction year. Incorporation of human‐related variables in SDM results in more accurate predictions for all species.

Assessing Niche Shifts and Conservatism by Comparing the Native and Post-Invasion Niches of Major Forest Invasive Species.

Invasive species experience biotic and abiotic conditions that may (or may not) resemble their native environment. We explored the methodology of determining climatic niches and compared the native and post-invasion niches of four invasive forest pests to determine if these species experienced shifts or changes in their new climatic niches. We used environmental principle components analysis (PCA-env) method to quantify climatic niche shifts, expansions, and temporal changes. Furthermore, we assessed the effect of variable selection in the delineation and comparison of niche space. We found that variable selection influenced the delineation and overlap of each niche, whereas the subset of climatic variables selected from the first two PCA-env axes explained more variance in environmental conditions than the complete set of climatic variables for all four species. Most focal species showed climatic niche shifts in their invasive range and had not yet fully occupied the available niche within the invaded range. Our species varied the proportion of niche overlap between the native and invasive ranges. By comparing native and invasive niches, we can help predict a species’ potential range expansion and invasion potential. Our results can guide monitoring and help inform management of these and other invasive species.

Specificity of 3D MSC Spheroids Microenvironment: Impact on MSC Behavior and Properties.

Mesenchymal stem cells (MSC) have been considered the promising candidates for the regenerative and personalized medicine due to their self-renewal potential, multilineage differentiation and immunomodulatory capacity. Although these properties have encouraged profound MSC studies in recent years, the majority of research has been based on standard 2D culture utilization. The opportunity to resemble in vivo characteristics of cells native niche has been provided by implementation of 3D culturing models such as MSC spheroid formation assesed through cells self-assembling. In this review, we address the current literature on physical and biochemical features of 3D MSC spheroid microenvironment and their impact on MSC properties and behaviors. Starting with the reduction in the cells' dimensions and volume due to the changes in adhesion molecules expression and cytoskeletal proteins rearrangement resembling native conditions, through the microenvironment shifts in oxygen, nutrients and metabolites gradients and demands, we focus on distinctive and beneficial features of MSC in spheroids compared to cells cultured in 2D conditions. By summarizing the data for 3D MSC spheroids regarding cell survival, pluripotency, differentiation, immunomodulatory activities and potential to affect tumor cells growth we highlighted advantages and perspectives of MSC spheroids use in regenerative medicine. Further detailed analyses are needed to deepen our understanding of mechanisms responsible for modified MSC behavior in spheroids and to set future directions for MSC clinical application.

Laminin-511-E8 promotes efficient in vitro expansion of human limbal melanocytes

Limbal melanocytes, located in the basal epithelial layer of the corneoscleral limbus, represent essential components of the corneal epithelial stem cell niche, but, due to difficulties in their isolation and cultivation, their biological roles and potential for stem cell-based tissue engineering approaches have not been comprehensively studied. Here, we established a protocol for the efficient isolation and cultivation of pure populations of human limbal melanocytes, which could be expanded at high yield by using recombinant laminin (LN)-511-E8 as culture substrate. Co-cultivation of limbal melanocytes with limbal epithelial stem/progenitor cells on fibrin hydrogels pre-incubated with LN-511-E8 resulted in multilayered stratified epithelial constructs within ten days. By reproducing physiological cell–cell and cell–matrix interactions of the native niche environment, these biomimetic co-culture systems provide a promising experimental model for investigating the functional roles of melanocytes in the limbal stem cell niche and their suitability for developing advanced epithelial grafts for ocular surface surface reconstruction.

Morphological changes and genome evolution in Raphidiopsis raciborskii CS-506 after 23 years in living culture

ABSTRACT Microscopic organisms maintained in long-term living monocultures undergo evolution, adapting to the stable laboratory environment. Culture adaptation can result in isolates no longer being representative of their native environmental niche. This study characterized the morphology and compared the full genomes of four daughter cultures of the toxic cyanobacterium Raphidiopsis raciborskii CS-506 maintained in living culture for 23 years. The four daughter cultures were split from the parent culture between 2 and 10 years ago. The morphotypes of two cultures had changed from coiled to straight (CS-506A, B), while CS-506C, D had smaller cells and shorter coiled trichomes. The toxin cell quota had increased for cultures CS-506A-C but decreased in CS-506D compared to 2012 measurements. Culture CS-506C was unable to produce heterocysts or fix atmospheric nitrogen. The core genome, comprising 78% of all genes and all primary metabolic functions, was unchanged. The variable genome, ~12%, showed difference in gene presence/absence, and ~1% of each genome was unique proteins, with evidence of horizontal gene transfer from contaminating bacteria and multiple gene loss events, and an overall strategy of genome reduction. The changes in morphology, nitrogen fixation and toxin cell quota were not supported by identifiable genome changes, with 100% synteny across nifHDK and cyr gene clusters. The results suggest that R. raciborskii CS-506 has a stable core genome, heritable phenotypes, and a variable genome generated through horizontal gene transfer and gene loss.

Microfluidic 3D Model of Heterochronic Parabiosis to Study Systemic Regulation of Skeletal Muscle Aging

Muscle satellite cells (MuSCs) play an indispensable role in skeletal muscle regeneration after injury. However, their regenerative capacity declines with aging. Intriguingly, studies using parabiosis, a surgical technique that attaches two animals to share blood circulation, demonstrated that circulating factors from young animals can rejuvenate the regenerative capacity of aged animals. However, the exact identity of these putative youthful factors has yet to be elucidated. Due to the complexity of in vivo parabiosis, reliable identification of systemic rejuvenation factors remains a major hurdle. To overcome this challenge, we employed microengineering technologies and developed a 3D microfluidic circuit with biophysical and biochemical properties similar to in vivo muscle microenvironment. Here, we present a 3D micro‐vascularized muscle‐on‐a‐chip (VMoC) that exhibits key characteristics of the native MuSC niche, where FACS purified quiescent MuSCs are cultured in between myofibers and 3D hydrogel (extracellular matrix mimetic) underneath vascular endothelial cells. With the VMoC, we further integrated it to model parabiosis by co‐culturing cells/sera from young and aged animals. By adding the serum from young, aged, and Sod1−/− (oxidative stress model) mice to VMoCs, we demonstrate distinct myogenic activities of young MuSCs; VMoCs with aged and Sod1−/− sera showed significantly reduced myogenesis as measured by fusion index. Next, we replicated heterochronic parabiosis using our integrated chip‐to‐chip platform to assess the rejuvenating effects of young serum/cells. Interestingly, similar to in vivo parabiosis, when aged VMoCs were continuously exposed to the young systemic environment, the myogenic activity of aged MuSCs were significantly boosted. In addition, genes that regulate different steps of adult myogenesis (Desmin, MyoD, and Myogenin) were up‐regulated in the aged VMoC exposed to the young systemic environment. Furthermore, this rejuvenation effect in myogenesis was correlated with increased VEGF, which has been shown to play a crucial role in MuSC function in parabiosed VMoC. Collectively, our parabiosis‐on‐a‐chip platform will provide a state‐of‐the‐art pre‐clinical testing tool that will facilitate our understanding of the dynamic regulation of circulating humoral factors and potential drug discovery. More importantly, our approach can be translated into human clinical studies by replacing the murine cells with the corresponding human cells, emulating human parabiosis on‐a‐chip that blood transfusion cannot recapitulate.Support or Funding InformationNIH R21AR072287 (YJ), NIH R03AG062976 (YJ), and NIH DP2HL142050 (YK)

Niche conservatism in a plant with long invasion history: the case of the Peruvian peppertree (Schinus molle, Anacardiaceae) in Mexico

Background and aim – Invasive plants should only colonize habitats meeting the environmental conditions included in their native niches. However, if they invade habitats with novel environmental conditions, this can induce shifts in their niches. This may occur in plants with long invasion histories because they interacted with the environmental conditions of invaded regions over long periods of time. We focused on this issue and evaluated whether the niche of the oldest plant invader reported in Mexico, the Peruvian peppertree, is still conserved after almost 500 years of invasion history. Methods – We compared climatic niches of the species between the native and invaded region. We later used species distribution models (SDM) to visualize the geographical expression of both niches in Mexico. Results – The invasive niche of the Peruvian peppertree is fully nested within the native niche. Although this suggests that the niche is conserved, this also indicates that a large fraction of the native niche is empty in the invaded region. The SDM from the native region indicated that Mexico contains habitats meeting the conditions included in this empty fraction of the native niche and, thus, this invasion should continue expanding. Nevertheless, the SDM calibrated with data from the invaded region indicated that peppertrees have colonized all suitable habitats indicated by its invasive niche and, thus, their populations should no longer expand. Conclusion – Our results suggests that the niche of the Peruvian peppertree is partially conserved in Mexico. This may have occurred because individuals introduced into Mexico constituted a small, nonrepresentative sample of the full niche of the species.

Matrix decoded – A pancreatic extracellular matrix with organ specific cues guiding human iPSC differentiation

The extracellular matrix represents a dynamic microenvironment regulating essential cell functions in vivo. Tissue engineering approaches aim to recreate the native niche in vitro using biological scaffolds generated by organ decellularization. So far, the organ specific origin of such scaffolds was less considered and potential consequences for in vitro cell culture remain largely elusive. Here, we show that organ specific cues of biological scaffolds affect cellular behavior. In detail, we report on the generation of a well-preserved pancreatic bioscaffold and introduce a scoring system allowing standardized inter-study quality assessment. Using multiple analysis tools for in-depth-characterization of the biological scaffold, we reveal unique compositional, physico-structural, and biophysical properties. Finally, we prove the functional relevance of the biological origin by demonstrating a regulatory effect of the matrix on multi-lineage differentiation of human induced pluripotent stem cells emphasizing the significance of matrix specificity for cellular behavior in artificial microenvironments.