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Transcriptomic characterisation of haematopoietic stem and progenitor cells from adult human spleen

ABSTRACT: Transcriptomic characterisation of haematopoietic stem and progenitor cells from adult human spleen

PROVIDER: PRJNA785654 | ENA |

REPOSITORIES: ENA

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Transcriptomic characterisation of haematopoietic stem and progenitor cells from adult human spleen

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

Transcriptomic characterisation of phenotypic haematopoietic stem cells from human adult bone marrow, spleen and peripheral blood

Project description:Transcriptomic characterisation of phenotypic haematopoietic stem cells from human adult bone marrow, spleen and peripheral blood

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Transcriptomic characterisation of phenotypic haematopoietic stem cells from human adult bone marrow, spleen and peripheral blood

Project description:Haematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), the precursors of all blood cells, reside predominantly in the bone marrow (BM). Recent evidence suggests that other anatomical sites may contribute significantly to blood production, but the cellular, molecular and functional composition of extramedullary HSC/MPP pools remains unexplored. Here, we have compared the transcriptomes of single cells sorted from the phenotypic HSC/MPP pool of adult bone marrows and spleens from the same donors.

2020-01-14 | GSE143567 | GEO

Transcriptomic characterisation of haematopoietic stem and progenitor cells from human adult bone marrow, spleen and peripheral blood

Project description: Not available

| S-SUBS4 | biostudies-other

Foetal and adult HSPCs - Comprehensive Proteomic Characterization of Ontogenic Changes in Hematopoietic Stem and Progenitor Cells

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

Transcriptional profiling of CML and normal, stem and progenitor haematopoietic cells.

Project description:Transcriptional profiling of four cell populations to understanding chronic myeloid leukaemia in humans. The populations are normal haematopoietic stem cells (HSC), normal progenitor cells (HPC), CML stem cells (LSC) and CML progenitor cells (LPC).

2016-05-26 | E-MTAB-2581 | biostudies-arrayexpress

Haematopoietic stem and progenitor cells are present in healthy gingiva tissue

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

Epoxyeicosatrienoic Acids Enhance Haematopoietic Stem and Progenitor Cell Specification and Engraftment

Project description:Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions including leukemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here, we developed a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We used this system to conduct a chemical screen and identified epoxyeicosatrienoic acids (EET) as a family of lipids that enhance HSPC engraftment. EETs’ pro-haematopoietic effects are conserved in the developing zebrafish, where this molecule promotes HSPC specification through activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect requires the activation of PI3K pathway, specifically PI3Kg. In adult HSPCs, EETs induce transcriptional programs including AP-1 activation, modulating multiple cellular processes, such as migration, to promote engraftment. Finally, we demonstrated that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study established a novel method to explore the molecular mechanisms of HSPC engraftment, and discovered a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.

2015-07-13 | GSE66767 | GEO

Conversion of adult endothelium to immunocompetent haematopoietic stem cells

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

Expression data from adult mouse spleen

Project description:Expression data from adult mouse spleen

| PRJNA633475 | ENA