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An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche [LCM-Seq]

ABSTRACT: An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche [LCM-Seq]

PROVIDER: PRJNA975088 | ENA |

REPOSITORIES: ENA

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An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche [LCM-Seq]

Project description:The emergence of definitive human haematopoietic stem cells (HSCs) during Carnegie Stages (CS) 14-17 in the aorta-gonad-mesonephros (AGM) region is a complex and tightly regulated process. In a previous study we conducted spatial transcriptomic analysis of the human AGM region at the end of this period (CS16/17) and identified secreted factors involved in HSC development. Here, we extend our analysis to investigate the progression of dorso-ventral polarized signalling around the dorsal aorta over the entire period of HSC emergence. Our results reveal a dramatic increase in signalling complexity from the CS13 to CS14 transition, coinciding with the activation of endothelial-to-haematopoietic transition (EHT) in the ventral domain of the dorsal aorta. We further observe stage-specific changes in signalling complexity up to CS17. Signalling progression described here may underpin step-wise maturation of HSCs described in the mouse model. A data-rich bioinformatics resource presented here along with an interactive online interface enables in silico analysis of molecular interactions between spatially defined domains of the AGM region. This resource will be of particular interest for researchers studying mechanisms underlying human HSC development as well as those developing in vitro methods for the generation of clinically relevant HSCs from pluripotent stem cells.

2023-10-31 | GSE233126 | GEO

An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche [scRNA-seq]

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An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche

Project description:An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche

| PRJNA975083 | ENA

An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche [scRNA-seq]

Project description:An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche [scRNA-seq]

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Label-free quantitative proteomics analysis of bone marrow cells of MK-LCM WT versus KO mice

Project description:High ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of hematopoietic stem cells (HSC) and are responsible for platelet formation. Using a mouse knockout model with normal megakaryocyte numbers but essentially devoid of LCM (MK-LCM KO), we demonstrated a pronounced increase in bone marrow HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. When HSC isolated from a MK-LCM KO microenvironment were transplanted in lethally irradiated mice, the absence of LCM increased HSC in BM, blood and spleen. Severe thrombocytopenia was observed in animals with diminished LCM, although there was no change in megakaryocyte ploidy distribution. In contrast, WT HSC-generated LCM regulated a normal HSC pool and prevented thrombocytopenia. The present label-free quantitative LC-MSMS data was used to determine proteins that are differentially expressed in bone marrow cells of MK-LCM WT versus MK-LCM KO mice.

2023-05-10 | PXD040423 | Pride

LCM-Seq analysis of microscopically defined human embryo HSC microenvironment

Project description:LCM-Seq analysis of microscopically defined human embryo HSC microenvironment

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An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-31 | GSE233132 | GEO

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).

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Project description:Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches, however whether the BM microenvironment plays a role in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and combining single cell RNA sequencing, mathematical modelling, transplantation assays and intravital microscopy, we show that haematopoiesis is reprogrammed upon infection, whereby the HSC compartment turns over significantly faster than in steady-state and HSC function is drastically affected as a result. Interferon is found to affect both haematopoietic and mesenchymal BM cells and we specifically identify a dramatic loss of osteoblasts and alterations in endothelial cell function. Osteo-active parathyroid hormone treatment abolishes infection-triggered HSC proliferation and, coupled with Reactive Oxygen Species quenching, enables partial rescuing of HSC function.

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