Single cell transcriptome landscape of human hematopoietic stem and progenitor cells during postnatal development
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157123 | GEO | 2026/03/01
REPOSITORIES: GEO
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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:Traditional single-cell RNA-seq technologies have shown limitations for large scale experiments. Here, we constructed a single-cell resolution transcriptomic atlas of (HSPCs) in human and mouse,including a total number of 71,729 single cells clustered into 39 subpopulations by computational analysis. In human, we found 20 progenitors primed with unique lineages like megakaryocyte, neutrophil and B cell progenitor can project directly from HSPCs. Within the c-Kit positive cells from mouse bone marrow, we described 19 progenitor subgroups at single cell resolution.
2018-05-18 | GSE92274 | GEO
Project description:Haematopoietic stem and progenitor cells (HSPCs) in the foetus and adult possess distinct molecular landscapes that regulate cell fate and change their susceptibility to initiation and progression of haematopoietic malignancies. The proteomic programs that govern these differences remain elusive. In this study, we have utilized a mass spectrometry-based quantitative proteomics approach to comprehensively describe and compare the proteome of foetal and adult HSPCs. We found that the proteome of foetal HSPCs is relatively simple, characterized by proteins involved in cell cycle and cell proliferation, while their adult counterparts are defined by a larger set of proteins that are involved in more diverse cellular processes. These adult characteristics include an arsenal of proteins important for viral and bacterial defence, as well as protection against ROS-induced protein oxidation. Our further analyses of Type I interferon signalling shows that foetal HSPCs are sensitive to Interferon a (IFNa), which impairs their production of mature lymphoid cells, whereas stimulation with IFNa to the pregnant mother enhances the production of early progenitors from foetal HSCs. Our results provide new and important insights into the molecular landscape of foetal and adult haematopoiesis that advance our understanding of normal and malignant haematopoiesis during foetal and adult life.
2017-12-12 | PXD006876 | Pride
Project description:Metabolic cues are crucial for regulating hematopoietic stem and progenitor cells (HSPCs). However, the metabolic profile of human HSPCs remains poorly understood due to the limited number of cells and the scarcity of bone marrow samples. Here, we present the integrated metabolome, lipidome and transcriptome of human adult HSPCs (lineage-, CD34+, CD38-) upon differentiation, aging and acute myeloid leukemia (AML). The combination of low-input targeted metabolomics with our newly optimized low-input untargeted lipidomics workflow allows us to detect up to 219 metabolites and lipids from a starting material of 3,000 and 5,000 HSPCs, respectively. Among other findings, we observe elevated levels of the essential nutrient choline in HSPCs compared to downstream progenitors, which decline upon aging and further decrease in AML. Functionally, we show that choline supplementation fuels lipid production in HSPCs and enhances stemness. Overall, our study provides a comprehensive resource identifying metabolic changes that can be utilized to promote and enhance human stem cell function.
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Project description:Metabolic cues are crucial for regulating hematopoietic stem and progenitor cells (HSPCs). However, the metabolic profile of human HSPCs remains poorly understood due to the limited number of cells and the scarcity of bone marrow samples. Here, we present the integrated metabolome, lipidome and transcriptome of human adult HSPCs (lineage-, CD34+, CD38-) upon differentiation, aging and acute myeloid leukemia (AML). The combination of low-input targeted metabolomics with our newly optimized low-input untargeted lipidomics workflow allows us to detect up to 219 metabolites and lipids from a starting material of 3,000 and 5,000 HSPCs, respectively. Among other findings, we observe elevated levels of the essential nutrient choline in HSPCs compared to downstream progenitors, which decline upon aging and further decrease in AML. Functionally, we show that choline supplementation fuels lipid production in HSPCs and enhances stemness. Overall, our study provides a comprehensive resource identifying metabolic changes that can be utilized to promote and enhance human stem cell function.
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Project description:Conserved and muscle group-specific gene expression patterns shape postnatal development of the novel extraocular muscle phenotype. Comparison of postnatal development of extraocular and hindlimb muscle between birth and P45.
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Project description:Mechanistic studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPC) through to mature naïve T cells. We developed a serum free, artificial thymic organoid (ATO) system that supports highly efficient and reproducible in vitro differentiation and positive selection to generate conventional human T cells from all sources of HSPCs. Deep-sequencing of the TCR variable genes was performed to compare the diversity of the TCR repertoire between ATO-derived CD8SP T cells and naive CD8SP T cells from thymus and blood.
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