Decoding functional haematopoietic progenitor cells in the adult human lung
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE255687 | GEO | 2025/02/07
REPOSITORIES: GEO
Dataset's files
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Project description:Haematopoietic stem and progenitor cells (HSPCs), the precursors of all blood cells, reside predominantly in the bone marrow. Yet, a small proportion (<1%) of phenotypic HSPCs is also found in extramedullary tissues, such as spleen, where they contribute to blood production under stress conditions. However, the detailed characterization of extramedullary HSPCs remains poor. Here, we analyse the single-cell composition of the adult human HSPC pool within the spleen from two patients with hereditary spherocytosis (HS), a disorders causing abnormal red blood cells. 10x scRNA-seq of CD19- CD34+ HSPCs was paired with single-cell functional analysis using most immature haematopoietic stem cells and multipotent progenitors (HSC/MPPs). We find that HSC/MPPs from HS spleens have a stronger transcriptional and functional bia towards the erythroid lineage than control sample.
2022-02-18 | GSE190067 | GEO
Project description:The bone marrow is classically viewed as the main site of blood cell production in adults, however, rare pools of haematopoietic stem and progenitor cells with self-renewal and differentiation potential have been described in extramedullary organs. The lung is primarily known for its role in gas exchange but has recently been identified as a site of blood (platelet) production in mice. Here, we show that functional haematopoietic precursors reside in the extravascular spaces of the human lung, at a frequency similar to the bone marrow, and are capable of proliferation and engraftment. Comparative transcriptomic profiling of pulmonary and medullary CD34+ haematopoietic progenitor cells revealed organ-specific gene signatures and indicated greater baseline activation of immune, megakaryocyte/platelet and erythroid-related pathways in progenitors from the lung. In the lung, these cells predominately reside in the vascular-rich alveolar interstitium and near macrophages. These results identify the lung as an important niche for uniquely programmed blood stem and progenitor cells with considerable potential to support haematopoiesis in humans.
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Project description:Background Differences in immune response between individuals is driven in part by epigenetic factors. To understand the contribution of DNA methylation to these differences, we have investigated the role of haematopoietic stem cell methylation in driving variation in daughter cell differentiation and state. Methods Haematopoietic cells (namely CD34+, CD14+ and CD56+) were isolated from peripheral blood of 11 healthy individuals and subject to modified reduced representation bisulfite sequencing. DNA methylation was profiled and compared at CpG islands. Results DNA methylation state is almost entirely recapitulated between progenitor and progeny haematopoietic cells. Fewer differences in DNA methylation were detected between haematopoietic cells than between haematopoietic cells and buccal mucosa. Cell subset differences in methylation were over-represented near genes important in cell lineage specific maturation and function. Methylation differences between individuals at specific CpG islands were generally small. The CpG islands that varied most between individuals consistently across subsets, were associated with several genes, but were not enriched with regard to specific biological processes. Conclusions Overall, this study suggests that the predominant DNA methylation setting in haematopoietic stem cells is transmitted to progeny cells, with differences between cell subsets and between individuals that are likely to be important in immune cell development and variation in response to pathogens and disease. Our findings provide a plausible mechanism by which genetic and environmental factors may contribute to the development of disease via unfavourable DNA methylation settings.
2020-09-30 | GSE114254 | GEO
Project description:Blood is generated by a constant stream of differentiating haematopoietic progenitor cells. The process is controlled by an immensely complex gene regulatory networks. These have been difficult to comprehend using correlative evidence and limited systematic functional data. Hoxb8-FL cell line is a model system of lympho-myeloid progenitors, which self-renews in vitro and is amenable to genetic perturbations. To construct a functionally defined transcription factor (TF) network we targeted 39 transcription factors using CRISPR/Cas9 gene targeting in Hoxb8-FL cells. We measured the resulting transcriptional changes by small scale RNA-Seq within 2-4 d of each perturbation. Our network analysis revealed >17,000 TF-target interactions across >7,000 target genes, established new interactions among TFs and shed new light on the mechanisms maintaining self-renewal and multipotency.
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Project description:This data presents the transcriptomes of bulk mature colonies derived from single human haematopoietic stem cells / multipotent progenitors (HSC/MPPs) and granulocyte macrophage progenitors (GMPs) purified from one indiviual with age related clonal haematopoisesis. The profiled colonies contain mature monocytes, as measured by conventional cell surface markers (CD14+, CD15-, GlyA-), but no other mature blood cell types. This dataset is part of a larger study, the main objective of which is to understand the functional effects conferred by somatic DNMT3A R882H mutation on human haematopoietic stem cell differentiation capacity. In clonal haematopoiesis, DNMT3A R882H and DNMT3A WT HSPCs co-exist in the same individual. We compared the transcriptional differences between mature monocytic colonies derived from DNMT3A R882H and WT HSPCs in vitro. Analysis of this dataset shows that, in this individual, DNMT3A R882H HSPCs produce less mature monocytes than their WT counterparts over the same culture time.
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Project description:Functional Dissection of Transcription Factor Networks Governing Haematopoietic Progenitor States
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Project description:Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders.
2017-05-18 | GSE88840 | GEO
Project description:In order to investigate the role of CD34 antigen in haematopoietic commitment, we silenced the CD34 gene expression in CD34+ stem/progenitor cells using a siRNA approach. Experiment Overall Design: To maximize siRNA transfection efficiency, we utilized the NucleofectorTM technology (Amaxa). CD34+ cells were transfected with a mixture of 4 siRNAs targeting CD34 mRNA and with a non-targeting siRNA as a negative control. The expression level of CD34 antigen on control cells (MOCK and negative control treated cells) and CD34siRNA treated cells was assessed by immunofluorescence analysis at 24 and 48h post-nucleofection.
2008-06-18 | E-GEOD-8002 | biostudies-arrayexpress
Project description:Haematopoietic stem cells reside in the bone marrow where they generate the effector cells that drive immune responses. However, in response to inflammation some haematopoietic stem and progenitor cells (HSPC) are recruited to tissue sites and undergo extramedullary haematopoiesis. Contrasting this paradigm here we show, with single cell sequencing, residence and differentiation of HSPC in healthy gingiva, a key oral barrier, in the absence of overt inflammation.
2021-02-23 | E-MTAB-10050 | biostudies-arrayexpress
Project description:Promoter capture Hi-C of CD34+ haematopoietic stem cells
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