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Developmental trajectory of pre-hematopoietic stem cell formation from endothelium (scATAC-seq data set)

ABSTRACT: Developmental trajectory of pre-hematopoietic stem cell formation from endothelium (scATAC-seq data set)

PROVIDER: PRJNA564577 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10087281_1.fastq.gz	Fastqsanger.gz
	SRR10087281_2.fastq.gz	Fastqsanger.gz
	SRR10087282_1.fastq.gz	Fastqsanger.gz
	SRR10087282_2.fastq.gz	Fastqsanger.gz
	SRR10087283_1.fastq.gz	Fastqsanger.gz

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Developmental trajectory of pre-hematopoietic stem cell formation from endothelium (scATAC-seq data set)

Project description:To examine the cell and molecular transitions between endothelial (E), hemogenic endothelial (HE), and intra-arterial clusters (IAC) cells, we profiled ~1700 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of embryonic day (E) 10.5 mouse embryos by single-cell ATAC sequencing (scATAC-Seq). We found extensive cis--regulatory landscape change during the endothelial to hematopoietic transition (EHT).

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Project description:To examine the cell and molecular transitions between endothelial (E), hemogenic endothelial (HE), and intra-arterial clusters (IAC) cells, and the heterogeneity of hematopoietic stem and progenitor cells (HSPCs) within the IACs, we profiled ~40,000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline arteries) of embryonic day (E) 9.5 to 11.5 mouse embryos by single-cell RNA sequencing (scRNA-Seq). We identified a developmental bottleneck in endothelial to hematopoietic transition (EHT) and heterogeneity within the IAC population.

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Developmental trajectory of pre-hematopoietic stem cell formation from endothelium

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Project description:Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the major arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters (IAC) before colonizing the fetal liver. To examine the cell and molecular transitions between endothelial (E), HE, and IAC cells, and the heterogeneity of HSPCs within IACs, we profiled ∼40 000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of 9.5 days post coitus (dpc) to 11.5 dpc mouse embryos by single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing. We identified a continuous developmental trajectory from E to HE to IAC cells, with identifiable intermediate stages. The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. A developmental bottleneck separates pre-HE from HE, with RUNX1 dosage regulating the efficiency of the pre-HE to HE transition. A distal candidate Runx1 enhancer exhibits high chromatin accessibility specifically in pre-HE cells at the bottleneck, but loses accessibility thereafter. Distinct developmental trajectories within IAC cells result in 2 populations of CD45+ HSPCs; an initial wave of lymphomyeloid-biased progenitors, followed by precursors of hematopoietic stem cells (pre-HSCs). This multiomics single-cell atlas significantly expands our understanding of pre-HSC ontogeny.

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