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Single cell mRNA sequencing of de novo hematopoiesis from the fetal lung

ABSTRACT: Single cell mRNA sequencing of de novo hematopoiesis from the fetal lung

PROVIDER: PRJNA809684 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18113101_1.fastq.gz	Fastqsanger.gz
	SRR18113101_2.fastq.gz	Fastqsanger.gz
	SRR18113102_1.fastq.gz	Fastqsanger.gz
	SRR18113102_2.fastq.gz	Fastqsanger.gz
	SRR18113103_1.fastq.gz	Fastqsanger.gz

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Single cell mRNA sequencing of de novo hematopoiesis from the fetal lung

Project description:Hemogenic endothelium, which gives rise to the earliest HSCs, is thought to be isolated to very early stages of development, peaking at E10.5 in mice. However, our data suggests there may be hemogenic endothelium capable of giving rise to de-novo HSPCs in the fetal lungs of mice at E17. We've adapted a platform to recapitulate the ex-vivo development of HSPCs from E17 lung endothelium. This sequencing experiment will help us to validate whether what we are seeing in culture is indeed endothelial to hematopoietic transition (EHT) and possibly identify the subset of endothelial cells that give rise to HSPCs.

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De novo hematopoiesis from the fetal lung.

Project description:Hemogenic endothelial cells (HECs) are specialized cells that undergo endothelial-to-hematopoietic transition (EHT) to give rise to the earliest precursors of hematopoietic progenitors that will eventually sustain hematopoiesis throughout the lifetime of an organism. Although HECs are thought to be primarily limited to the aorta-gonad-mesonephros (AGM) during early development, EHT has been described in various other hematopoietic organs and embryonic vessels. Though not defined as a hematopoietic organ, the lung houses many resident hematopoietic cells, aids in platelet biogenesis, and is a reservoir for hematopoietic stem and progenitor cells (HSPCs). However, lung HECs have never been described. Here, we demonstrate that the fetal lung is a potential source of HECs that have the functional capacity to undergo EHT to produce de novo HSPCs and their resultant progeny. Explant cultures of murine and human fetal lungs display adherent endothelial cells transitioning into floating hematopoietic cells, accompanied by the gradual loss of an endothelial signature. Flow cytometric and functional assessment of fetal-lung explants showed the production of multipotent HSPCs that expressed the EHT and pre-HSPC markers EPCR, CD41, CD43, and CD44. scRNA-seq and small molecule modulation demonstrated that fetal lung HECs rely on canonical signaling pathways to undergo EHT, including TGFβ/BMP, Notch, and YAP. Collectively, these data support the possibility that post-AGM development, functional HECs are present in the fetal lung, establishing this location as a potential extramedullary site of de novo hematopoiesis.

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