Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta

Chloé S Baron; Lennart Kester; Anna Klaus; Jean-Charles Boisset; Roshana Thambyrajah; Laurent Yvernogeau; Valérie Kouskoff; Georges Lacaud; Alexander van Oudenaarden; Catherine Robin

doi:10.1038/s41467-018-04893-3

Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta

Chloé S Baron, Lennart Kester, Anna Klaus, Jean-Charles Boisset, Roshana Thambyrajah, Laurent Yvernogeau, Valérie Kouskoff, Georges Lacaud, Alexander van Oudenaarden, Catherine Robin

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

97 Citaten (Scopus)

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Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders.

Originele taal-2	Engels
Pagina's (van-tot)	2517
Tijdschrift	Nature Communications
Volume	9
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-018-04893-3
Status	Gepubliceerd - 28 jun. 2018

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title = "Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta",

abstract = "Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders.",

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AU - Kester, Lennart

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AU - Boisset, Jean-Charles

AU - Thambyrajah, Roshana

AU - Yvernogeau, Laurent

AU - Kouskoff, Valérie

AU - Lacaud, Georges

AU - van Oudenaarden, Alexander

AU - Robin, Catherine

PY - 2018/6/28

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N2 - Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders.

AB - Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders.

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KW - Cell Differentiation

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KW - Female

KW - Gene Expression Regulation, Developmental

KW - Gene Ontology

KW - Gene Regulatory Networks

KW - Hemangioblasts/cytology

KW - Hematopoietic Stem Cells/cytology

KW - Mice

KW - Mice, Inbred C57BL

KW - Molecular Sequence Annotation

KW - Single-Cell Analysis

KW - Transcriptome

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Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta

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