Functional Niche Research Articles

Hydrogel microenvironment contributes to chemical-induced differentiation of mesenchymal stem cells: single-cell infrared microspectroscopy characterization.

Stem cell microenvironment plays vital roles in directing cell proliferation and differentiation. Due to the tiny biochemical changes in the early stage of stem cell development, technical challenges to characterize the potential effects of environmental signals remain. In this work, we have introduced synchrotron radiation-based Fourier transform infrared microspectroscopy to evaluate the synergistic effects of physical and chemical factors on stem cell differentiation at the single-cell level. By using principal component analysis and cell-cell Euclidean distance calculation, the phenotypic heterogeneity changes during stem cell osteogenesis induced by lithium chloride or Wnt5a protein loaded in the polyvinyl alcohol (PVA) hydrogel were characterized in detail. The results demonstrated that PVA hydrogel could lead to the distinct effects between low-concentration lithium and wnt5a on human mesenchymal stem cells, suggesting a vital role of niche signals in Wnt pathway. These findings highlight the importance of microenvironment to the chemical-induced effects on stem cell differentiation and also provide a label-free, noninvasive method to sensitively identify the niche function in stem cell biology.

Temperate functional niche availability not resident-invader competition shapes tropicalisation in reef fishes

Temperate reefs are at the forefront of warming-induced community alterations resulting from poleward range shifts. This tropicalisation is exemplified and amplified by tropical species’ invasions of temperate herbivory functions. However, whether other temperate ecosystem functions are similarly invaded by tropical species, and by what drivers, remains unclear. We examine tropicalisation footprints in nine reef fish functional groups using trait-based analyses and biomass of 550 fish species across tropical to temperate gradients in Japan and Australia. We discover that functional niches in transitional communities are asynchronously invaded by tropical species, but with congruent invasion schedules for functional groups across the two hemispheres. These differences in functional group tropicalisation point to habitat availability as a key determinant of multi-species range shifts, as in the majority of functional groups tropical and temperate species share functional niche space in suitable habitat. Competition among species from different thermal guilds played little part in limiting tropicalisation, rather available functional space occupied by temperate species indicates that tropical species can invade. Characterising these drivers of reef tropicalisation is pivotal to understanding, predicting, and managing marine community transformation.

Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response

Aging associated defects within stem cell-supportive niches contribute towards age-related decline in stem cell activity. However, mechanisms underlying age-related niche defects, and whether restoring niche function can improve stem cell fitness, remain unclear. Here, we sought to determine whether aged blood stem cell function can be restored by rejuvenating their supportive niches within the bone marrow (BM). We identify Netrin-1 as a critical regulator of BM niche cell aging. Niche-specific deletion of Netrin-1 induces premature aging phenotypes within the BM microenvironment, while supplementation of aged mice with Netrin-1 rejuvenates aged niche cells and restores competitive fitness of aged blood stem cells to youthful levels. We show that Netrin-1 plays an essential role in maintaining active DNA damage responses (DDR), and that aging-associated decline in niche-derived Netrin-1 results in DNA damage accumulation within the BM microenvironment. We show that Netrin-1 supplementation is sufficient to resolve DNA damage and restore regenerative potential of the aged BM niche and blood stem cells to endure serial chemotherapy regimens.

Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option

AbstractAlthough tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38– cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.

Restoring carboxypeptidase E rescues BDNF maturation and neurogenesis in aged brains

Abstract Adult neurogenesis declines with age due to the less functional neural stem cells (NSCs) and niches, but the underlying molecular bases for this impaired condition remain unclear. Here we analyzed >55,000 single-cell transcriptomes from two discrete neurogenic niches across the mouse lifespan, and identified new features and populations in NSCs, new markers, and neurogenic regional-specific alternations during aging. Intercellular communication analysis revealed defects in brain-derived neurotrophic factor (BDNF)-TrkB signaling cascade in old NSCs. Carboxypeptidase E (CPE) was found to be highly enriched in NSCs, and played a crucial role in mature/proBDNF balance and adult neurogenesis. Diminishment of CPE with aging resulted in impaired generation of BDNF, thus limiting the neurogenesis in old neurogenic niches. Restoring CPE expression markedly rescued the adult neurogenesis by increasing the production of mature BDNF, offering an attractive therapeutic strategy for the treatment of certain disorders in regions associated with constitutive neurogenesis.

Three-Dimensional Human Bone Marrow Organoids for the Study and Application of Normal and Abnormal Hematoimmunopoiesis.

Hematoimmunopoiesis takes place in the adult human bone marrow (BM), which is composed of heterogeneous niches with complex architecture that enables tight regulation of homeostatic and stress responses. There is a paucity of representative culture systems that recapitulate the heterogeneous three-dimensional (3D) human BM microenvironment and that can endogenously produce soluble factors and extracellular matrix that deliver culture fidelity for the study of both normal and abnormal hematopoiesis. Native BM lymphoid populations are also poorly represented in current invitro and invivo models, creating challenges for the study and treatment of BM immunopathology. BM organoid models leverage normal 3D organ structure to recreate functional niche microenvironments. Our focus herein is to review the current state of the art in the use of 3D BM organoids, focusing on their capacities to recreate critical quality attributes of the invivo BM microenvironment for the study of human normal and abnormal hematopoiesis.

MP01-03 XENO-FREE PEPTIDE-FUNCTIONALIZED BIOINKS IMPROVE EX VIVO CULTURE OF HUMAN TESTICULAR TISSUES

You have accessJournal of UrologyCME1 Apr 2023MP01-03 XENO-FREE PEPTIDE-FUNCTIONALIZED BIOINKS IMPROVE EX VIVO CULTURE OF HUMAN TESTICULAR TISSUES Meghan Robinson and Ryan Flannigan Meghan RobinsonMeghan Robinson More articles by this author and Ryan FlanniganRyan Flannigan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The development of human in vitro spermatogenesis (IVS) is a promising regenerative platform for the treatment of male factor infertility. IVS has been demonstrated in rodent models, but despite decades of research remains a challenge in the human sphere. A promising strategy may be to culture fragments of testis tissues in hydrogels. Hydrogels can be functionalized to sequester matrix and signaling peptides in a local manner mimicking tissue niche function. In this study we investigated the use of xeno-free hydrogels functionalized with biomimetic peptide motifs for their ability to improve ex vivo culture of human testicular tissues. METHODS: Human testicular tissues were obtained from hormone-treated gender affirmation patients following informed consent, gently teased apart, cut into small fragments and mixed into bioinks (VitroInk) containing either YIGSR (laminin), COL (collagen), or MMPs (matrix metalloproteinases) peptide motifs, then printed into ∼1 cm3 droplets using a BioX6 extrusion bioprinter (Figure 1A). 1 mL of media was placed on each and they were cultured in 34°C at 5% CO2 and ambient oxygen (21%) for 12 days, with 50% media changes every other day. The media consisted of Human Plasma-Like Medium (HPLM) with 15% CTS™ KnockOut™ SR XenoFree Medium, vitamins, metabolites, antioxidants, growth factors and hormones known to be present in the testis niche. Tissues were analyzed after 12 days by quantitative real-time polymerase chain reaction (qPCR) for gene expression associated with apoptosis, somatic cell function, spermatogonial stem cell maintenance, and spermatogenesis. RESULTS: After 12 days gene expression associated with somatic cell function and spermatogenesis was higher than suspension culture controls in all hydrogel groups (Figure 1B). Compared to freshly harvested testicular tissues, COL- and YIGSR-functionalized hydrogels exhibited similar expression levels of genes associated with somatic cell function, and the highest increased levels of genes associated with early spermatogenesis (Figure 1B). CONCLUSIONS: COL- or YIGSR peptide-functionalized hydrogels sustain testicular tissue function ex vivo in short-term cultures, whereas suspension culture exhibited tissue function loss, suggesting the utility of functionalized hydrogels for human IVS. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Meghan Robinson More articles by this author Ryan Flannigan More articles by this author Expand All Advertisement PDF downloadLoading ...

Smooth muscle contributes to the development and function of a layered intestinal stem cell niche.

Wnt and Rspondin (RSPO) signaling drives proliferation, and bone morphogenetic protein inhibitors (BMPi) impede differentiation, of intestinal stem cells (ISCs). Here, we identify the mouse ISC niche as a complex, multi-layered structure that encompasses distinct mesenchymal and smooth muscle populations. In young and adult mice, diverse sub-cryptal cells provide redundant ISC-supportive factors; few of these are restricted to single cell types. Niche functions refine during postnatal crypt morphogenesis, in part to oppose the dense aggregation of differentiation-promoting BMP+ sub-epithelial myofibroblasts at crypt-villus junctions. Muscularis mucosae, a specialized muscle layer, first appears during this period and supplements neighboring RSPO and BMPi sources. Components of this developing niche are conserved in human fetuses. The invivo ablation of mouse postnatal smooth muscle increases BMP signaling activity, potently limiting a pre-weaning burst of crypt fission. Thus, distinct and progressively specialized mesenchymal cells together create the milieu that is required to propagate crypts during rapid organ growth and to sustain adult ISCs.

Professional Pledge in Social Work: Implications for Professional Identity and Value Integration

The social work profession lays a strong emphasis on internalizing and reinforcing core social work values and ethical standards in order to create a cadre of social workers who can withstand the criticalities of any crisis and commit themselves to firmly stand with those whose survival and well-being is fragile and “on the brink”. The performance of this role not only requires a dynamic and contextual knowledge base and evolving skills set, it mandates a deep rooted acquiescence with a fundamental set of values that shape the profession’s vision and mission, and establish the goals and priorities of the practitioners. The transition from an entry level neophyte to a competent social work professional entails a journey which is characterized by the assumption and bolstering of a professional persona that grounds the incumbent within the functional niche of social work. The present paper looks at the integration of a social work pledge as a viable means for social work incumbents to establish identification with social work values, don a professional identity, and assimilate with professional peers. It looks at the existing practice of pledge taking by highlighting the experience of a distinguished school of social work. It envisions the ‘pledge’ and the tradition of ‘taking the pledge’ evolving as a strong and more universal medium for creating an emotional connect of social work students with the value driven profession of social work. Keywords: Pledge, values, ethics, social work, profession

Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment.

Systemic transplantation of mesenchymal stem cells (MSCs), such as bone marrow MSCs (BMMSCs) and stem cells from human exfoliated deciduous teeth (SHED), is considered a prominent treatment for osteopenia. However, the mechanism of action of the transplanted MSCs has been poorly elucidated. In the recipient target tissue, including bone and bone marrow, only a few donor MSCs can be detected, suggesting that the direct contribution of donor MSCs may not be expected for osteopenia treatment. Meanwhile, secretomes, especially contents within extracellular vesicles (EVs) released from donor MSCs (MSC-EVs), play key roles in the treatment of several diseases. In this context, administrated donor MSC-EVs may affect bone-forming function of recipient cells. In this review, we discuss how MSC-EVs contribute to bone recovery recipient tissue in osteopenia. We also summarize a novel mechanism of action of systemic administration of SHED-derived EVs (SHED-EVs) in osteopenia. We found that reduced telomerase activity in recipient BMMSCs caused the deficiency of microenvironmental modulating function, including bone and bone marrow-like niche formation and immunomodulation in estrogen-deficient osteopenia model mice. Systemic administration of SHED-EVs could exert therapeutic effects on bone reduction via recovering the telomerase activity, leading to the rejuvenation of the microenvironmental modulating function in recipient BMMSCs, as seen in systemic transplantation of SHED. RNase-preconditioned donor SHED-EVs diminished the therapeutic benefits of administrated SHED-EVs in the recipient osteopenia model mice. These facts suggest that MSC-EV therapy targets the recipient BMMSCs to rejuvenate the microenvironmental modulating function via telomerase activity, recovering bone density. We then introduce future challenges to develop the reproducible MSC-EV therapy in osteopenia.

Functional structure and interactions within communities composed of cover crops and spontaneous species, along a cropping practices gradient

Inclusion of a cover crop is an interesting way to diversify cropping systems and support ecosystem functions and services impaired by intensified monocultures. However, pure covers are hard to obtain without substantial management, and mixed covers—wherein some spontaneous species coexist with sown cover crops—seem to be a good alternative. Greater insight into factors influencing the composition and density of the spontaneous plant community is needed to achieve relatively good control of the performances of this mixed cover. Here we addressed two questions: 1) How does the functional structure of communities with a highly competitive sown cover crop and/or high initial species diversity differ from the functional structure of communities with the opposite characteristics? 2) Can aboveground species traits explain interactions between cover crops and spontaneous species present in the same community? In a fallowed field in Guadeloupe (West French Indies), we studied communities composed of one sown cover crop species and spontaneous species growing simultaneously in the plot. The study was conducted along two unrelated experimentally-devised gradients resulting from cropping practices: a competitivity gradient of a sown cover crop species and an initial species diversity gradient resulting from an initial soil perturbation induced by the false seedbed technique. These factors (soil tillage modality before cover crop sowing and cover crop species identity) were combined in a split-plot design. Seven and twelve months after cover crop sowing, community species densities and biomasses were assessed. Leaf trait values of the 12 most present species were measured at flowering to describe the functional structure of the community using the community weighted trait means and variances, and a functional diversity index. Our results showed high functional divergence in communities with highly competitive cover crops, which suggests differentiation of functional niches between species, but no clear differences in communities with high and low initial species diversity. We also showed that the studied species were positioned along a gradient from acquisitive to conservative strategies of resource capture and use according to their leaf trait values, regardless of their type (cover crops or spontaneous species), and that cover crop species had higher trait values related to size than spontaneous species. Finally, we demonstrated that interactions between cover crops and spontaneous species could be better explained by the cover crop dynamic height or community biomasses than by the measured aboveground functional traits and that the plant growth habit had a central role. This study shed light on interactions between sown cover crops and spontaneous species, which are pivotal to the design of diversified cropping systems.

Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells

Sinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone marrow hematopoietic niche, the oxygen tension is usually very low, and this condition affects stem and progenitor cell proliferation and differentiation and other important functions of this region. Here, we have investigated in vitro the response of endothelial cells to a marked decrease in O2 partial pressure to understand how the basal gene expression of some relevant biological factors (i.e., chemokines and interleukins) that are fundamental for the intercellular communication could change in anoxic conditions. Interestingly, mRNA levels of CXCL3, CXCL5, and IL-34 genes are upregulated after anoxia exposure but become downmodulated by sirtuin 6 (SIRT6) overexpression. Indeed, the expression levels of some other genes (such as Leukemia Inhibitory Factor (LIF)) that were not significantly affected by 8 h anoxia exposure become upregulated in the presence of SIRT6. Therefore, SIRT6 mediates also the endothelial cellular response through the modulation of selected genes in an extreme hypoxic condition.

O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors.

In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.

Salinity Alleviation and Reduction in Oxidative Stress by Endophytic and Rhizospheric Microbes in Two Rice Cultivars.

Increased soil salinity poses serious limitations in crop yield and quality; thus, an attempt was made to explore microbial agents to mitigate the ill effects of salinity in rice. The hypothesis was mapping of microbial induction of stress tolerance in rice. Since the rhizosphere and endosphere are two different functional niches directly affected by salinity, it could be very crucial to evaluate them for salinity alleviation. In this experiment, endophytic and rhizospheric microbes were tested for differences in salinity stress alleviation traits in two rice cultivars, CO51 and PB1. Two endophytic bacteria, Bacillus haynesii 2P2 and Bacillus safensis BTL5, were tested with two rhizospheric bacteria, Brevibacterium frigoritolerans W19 and Pseudomonas fluorescens 1001, under elevated salinity (200 mM NaCl) along with Trichoderma viride as an inoculated check. The pot study indicated towards the presence of variable salinity mitigation mechanisms among these strains. Improvement in the photosynthetic machinery was also recorded. These inoculants were evaluated for the induction of antioxidant enzymes viz. CAT, SOD, PO, PPO, APX, and PAL activity along with the effect on proline levels. Modulation of the expression of salt stress responsive genes OsPIP1, MnSOD1, cAPXa, CATa, SERF, and DHN was assessed. Root architecture parameters viz. cumulative length of total root, projection area, average diameter, surface area, root volume, fractal dimension, number of tips, and forks were studied. Confocal scanning laser microscopy indicated accumulation of Na+ in leaves using cell impermeant Sodium Green™, Tetra (Tetramethylammonium) Salt. It was found that each of these parameters were induced differentially by endophytic bacteria, rhizospheric bacteria, and fungus, indicating different paths to complement one ultimate plant function. The biomass accumulation and number of effective tillers were highest in T4 (Bacillus haynesii 2P2) plants in both cultivars and showed the possibility of cultivar specific consortium. These strains and their mechanisms could form the basis for further evaluating microbial strains for climate-resilient agriculture.

Standard ecological and molecular research methods and techniques for Labyrinthula spp.

Labyrinthula are unicellular protists occupying diverse spatial and functional niches, including various roles in host and ecological function, fatty acid production, pandemic marine disease and saprobic decomposition. Labyrinthula species span tropical and temperate climates and have been isolated from each marine coastal ecosystem tested. Our understanding of primary cellular and molecular functions of Labyrinthula has substantially progressed through a combination of increased global investments, research interest and technological advances. Recent advances in molecular techniques provide a toolkit for advancing ecological questions in marine infectious disease in seagrass meadows around the world. Here we provide a comprehensive review of relevant ecological and molecular techniques used in long-term research and the progression of Labyrinthula scholarship. Our aims in preparing this review are to: 1) share, compare and advance global Labyrinthula protocols, 2) increase accessibility to robust methodology to encourage the uptake of Labyrinthula-based questions into marine studies of molecular and ecological qualities of Labyrinthula and 3) encourage uptake of robust Labyrinthula-based questions into coastal marine studies, while also encouraging international collaborative networks across multiple fields. Lastly, we discuss gaps in the over 100 years of Labyrinthula research and opportunities for expanding research on this model marine organism.

A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11+ mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2+ non-chondrogenic fibroblasts instead of Chad+ chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury.

Deep time extinction of largest insular ant predators and the first fossil Neoponera (Formicidae: Ponerinae) from Miocene age Dominican amber

BackgroundPonerine ants are almost exclusively predatory and comprise many of the largest known ant species. Within this clade, the genus Neoponera is among the most conspicuous Neotropical predators. We describe the first fossil member of this lineage: a worker preserved in Miocene-age Dominican amber from Hispaniola.ResultsNeoponera vejestoria sp. nov. demonstrates a clear case of local extinction—there are no known extant Neoponera species in the Greater Antilles. The species is attributable to an extant and well-defined species group in the genus, which suggests the group is older than previously estimated. Through CT scan reconstruction and linear morphometrics, we reconstruct the morphospace of extant and fossil ants to evaluate the history and evolution of predatory taxa in this island system.ConclusionsThe fossil attests to a shift in insular ecological community structure since the Miocene. The largest predatory taxa have undergone extinction on the island, but their extant relatives persist throughout the Neotropics. Neoponera vejestoria sp. nov. is larger than all other predatory ant workers known from Hispaniola, extant or extinct. Our results empirically demonstrate the loss of a functional niche associated with body size, which is a trait long hypothesized to be related to extinction risk.

A mysterious triangle of blood, bones, and nerves.

The relationship between bone tissue and bone marrow, which is responsible for hematopoiesis, is inseparable. Osteoblasts and osteocytes, which produce and consist of bone tissue, regulate the function of hematopoietic stem cells (HSC), the ancestors of all hematopoietic cells in the bone marrow. The peripheral nervous system finely regulates bone remodeling in bone tissue and modulates HSC function within the bone marrow, either directly or indirectly via modification of the HSC niche function. Peripheral nerve signals also play an important role in the development and progression of malignant tumors (including hematopoietic tumors) and normal tissues, and peripheral nerve control is emerging as a potential new therapeutic target. In this review, we summarize recent findings on the linkage among blood system, bone tissue, and peripheral nerves.

Endoderm-derived islet1-expressing cells differentiate into endothelial cells to function as the vascular HSPC niche in zebrafish.

Endothelial cells (ECs) line blood vessels and serve as a niche for hematopoietic stem and progenitor cells (HSPCs). Recent data point to tissue-specific EC specialization as well as heterogeneity; however, it remains unclear how ECs acquire these properties. Here, by combining live-imaging-based lineage-tracing and single-cell transcriptomics in zebrafish embryos, we identify an unexpected origin for part of the vascular HSPC niche. We find that islet1 (isl1)-expressing cells are the progenitors of the venous ECs that constitute the majority of the HSPC niche. These isl1-expressing cells surprisingly originate from the endoderm and differentiate into ECs in a process dependent on Bmp-Smad signaling and subsequently requiring npas4l (cloche) function. Single-cell RNA sequencing analyses show that isl1-derived ECs express a set of genes that reflect their distinct origin. This study demonstrates that endothelial specialization in the HSPC niche is determined at least in part by the origin of the ECs.

4 - Paneth Cell Niche Function Is Dispensable in Gvhd

4 - Paneth Cell Niche Function Is Dispensable in Gvhd