A Single-Cell Resolution Atlas of expanding hematopoietic organ in zebrafish
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE146404 | GEO | 2021/03/18
REPOSITORIES: GEO
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Project description:A Single-Cell Resolution Atlas of expanding hematopoietic organ in zebrafish
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Project description:To characterize the distinct features of HSPCs and relevant niche cells, we performed RNA-seq with sorted zebrafish HSPCs and niche cells, based on fluorescent protein labeling from distinct regions at six relatively discrete stages.
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Project description:To investigate the peculiarity of CHT HSPCs, as well as the interaction of CHT niche and HSPCs at higher resolution, we performed scRNA-seq with zebrafish CHT.
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Project description:During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Furthermore, we investigated the regulatory mechanism of CHT niche components for HSPC development, with a focus on the transcription factors and ligand-receptor networks involved in HSPC expansion. Importantly, we identified an endothelial cell-specific G protein-coupled receptor 182, followed by in vivo and in vitro functional validation of its evolutionally conserved role in supporting HSPC expansion in zebrafish and mice. Finally, comparison between zebrafish CHT and human fetal liver highlighted the conservation and divergence across evolution. These findings enhance our understanding of the regulatory mechanism underlying hematopoietic niche for HSPC expansion in vivo and provide insights into improving protocols for HSPC expansion in vitro.
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Project description:Bone marrow inflammation has been linked to acute myeloid leukemia (AML) progression. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche, but the involvment of normal hematopoietic stem and progenitor cells (HSPCs) in the inflammatory crosstalk is not well understood. To better model compartmental inflammation in AML, we first established a highly penetrant, immunocompetent, fully congenic system. Using the monoblastic AML cell line C1498 (CD45.2+), we grafted non-condition C57BL/6J (CD45.1) mice, avoiding changes in BM niche function. We then fluoresence-activated cell sorting (FACS)-sorted residual normal HSPCs for single-cell RNA-sequencing analysis. We show that residual normal HSPCs from C1498-grafted mice expresses key inflammatory signature and are enriched in inflammatory signaling related pathways. Overall, we show that normal HSPCs engages in inflammatory signaling in AML niche.
2024-01-01 | GSE238091 | GEO
Project description:BackgroundThe vertebrate craniofacial skeleton may exhibit anatomical complexity and diversity, but its genesis and evolution can be understood through careful dissection of developmental programs at cellular resolution. Resources are lacking that include introductory overviews of skeletal anatomy coupled with descriptions of craniofacial development at cellular resolution. In addition to providing analytical guidelines for other studies, such an atlas would suggest cellular mechanisms underlying development.DescriptionWe present the Fish Face Atlas, an online, 3D-interactive atlas of craniofacial development in the zebrafish Danio rerio. Alizarin red-stained skulls scanned by fluorescent optical projection tomography and segmented into individual elements provide a resource for understanding the 3D structure of the zebrafish craniofacial skeleton. These data provide the user an anatomical entry point to confocal images of Alizarin red-stained zebrafish with transgenically-labelled pharyngeal arch ectomesenchyme, chondrocytes, and osteoblasts, which illustrate the appearance, morphogenesis, and growth of the mandibular and hyoid cartilages and bones, as viewed in live, anesthetized zebrafish during embryonic and larval development. Confocal image stacks at high magnification during the same stages provide cellular detail and suggest developmental and evolutionary hypotheses.ConclusionThe FishFace Atlas is a novel learning tool for understanding craniofacial skeletal development, and can serve as a reference for a variety of studies, including comparative and mutational analyses.
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Project description:Fetal hematopoietic stem and progenitor cells (HSPCs) migrate from fetal liver (FL) to bone marrow (BM) around birth. While adult BM HSPCs and their extrinsic regulation is well studied, little is known about the composition, function, and extrinsic regulation of the first HSPCs to enter the BM. Here, we show that HSPCs colonize multiple fetal bones by E15.5, shift from an MPP2 to an MPP3/4-dominant phenotype by birth, and display little function until E18.5, relative to their FL counterparts. We establish a transcriptional atlas of single perinatal HSPCs, and their putative BM niches, from E15.5 through P0 and show that early fetal BM (FBM) lacks HSPCs with intrinsic stem cell programs and niche cells supportive of HSPCs. In contrast, stem cell programs are preserved in neonatal BM HSPCs, which engage with a niche expressing HSC supportive factors distinct from those seen in adult BM (i.e., IGF).
2021-06-26 | GSE178951 | GEO
Project description:Hematopoietic stem and progenitor cells (HSPCs) rely upon cellular crosstalk, including extracellular vesicles (EVs) for lifelong niche occupancy and cellular function. Vesicle secretion is tightly linked to intracellular homeostasis; however, these mechanisms are poorly understood in HSPCs, particularly at the single-cell level. In this study, we target ceramide-dependent EV secretion by pharmacologic blockade in ex vivo expanded HSPCs. We use these cells to investigate single-cell resolution of short-term and delayed transcriptional changes induced by ceramide-EV inhibition.
2023-10-01 | GSE226348 | GEO
Project description:Inflammation in the bone marrow (BM) microenvironment is a constitutive component of acute myeloid leukemia (AML) pathogenesis. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche. Our recent studies in a congenic AML model suggest residual healthy hematopoietic stem and progenitor cells (HSPCs) participate in the inflammatory crosstalk. However, the underlying mechanism that drives the inflammatory conversion of HSPCs remains unclear. Here, we ask whether AML-derived extracellular vesicles (EV-AML) can convert HSPCs into an inflammatory active state in vivo. Using EV-AML purified from inducible (i)MLL-AF9 AML blasts (AF9-EV-AML), we challenged healthy C57BL/6J mice with serial injections of AF9-EVAML and analyzed HSPCs transcriptome. We show that HSPC transcriptome corroborates the enrichment of inflammatory and innate immune responses in EVAML-challenged BM HSPCs compared to controls. Our findings suggest that AML converts HSPCs into an inflammatory hub via EVAML in the AML niche.
2024-04-24 | GSE239307 | GEO
Project description:Ageing is associated with changes in the cellular composition of the immune system. During ageing, hematopoietic stem and progenitor cells (HSPCs) that produce immune cells are thought to decline in their regenerative capacity. However, HSPC function has been mostly assessed using transplantation assays, and it remains unclear how HSPCs age in the native bone marrow niche. To address this issue, we present a novel in situ single cell lineage tracing technology to quantify the clonal composition and cell production of single cells in their native niche. Our results demonstrate that a pool of HSPCs with unequal output maintains myelopoiesis through overlapping waves of cell production throughout adult life. During ageing, the increased frequency of myeloid cells is explained by greater numbers of HSPCs contributing to myelopoiesis, rather than increased myeloid output of individual HSPCs. Strikingly, the myeloid output of HSPCs remained remains constant over time despite accumulating significant transcriptomic changes throughout adulthood. Together, these results show that, unlike emergency myelopoiesis post-transplantation, aged HSPCs in their native microenvironment do not functionally decline in their regenerative capacity. This repository contains single-cell RNA sequencing datasets of hematopoietic stem and progenitor cells from young and aged mice associated with this study
2023-02-27 | GSE226131 | GEO