Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells

Chris Sebastiaan Vink; Fernando Jose Calero-Nieto; Xiaonan Wang; Antonio Maglitto; Samanta Antonella Mariani; Wajid Jawaid; Berthold Göttgens; Elaine Dzierzak

doi:10.1016/j.celrep.2020.107627

Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells

Chris Sebastiaan Vink, Fernando Jose Calero-Nieto, Xiaonan Wang, Antonio Maglitto, Samanta Antonella Mariani, Wajid Jawaid, Berthold Göttgens, Elaine Dzierzak

Research output: Contribution to journal › Article › peer-review

Abstract

Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single cell transcriptomics and functional analyses to connect HSC identity to specific gene expression.
Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit and CD27 phenotypic parameters that associate specific
molecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.

Original language	English
Article number	107627
Journal	Cell Reports
Volume	31
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2020.107627
Publication status	Published - 12 May 2020

Keywords

AGM
CD27
Gata2
development
embryo
functional identity
hematopoietic stem cell
heterogeneity
intra-aortic hematopoietic clusters
single-cell transcriptome
transplantation

Access to Document

10.1016/j.celrep.2020.107627Licence: Creative Commons: Attribution Non-Commercial (CC-BY-NC)

Published Version
This is an open access article under the CC BY-NC-ND license
Final published version, 4.63 MBLicence: Creative Commons: Attribution Non-Commercial (CC-BY-NC)

https://pubmed.ncbi.nlm.nih.gov/32402290/

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1 Finished
1 Active

Single cell hematopoietic fate acquisition during embryonic development: To be a stem cell or not?
Dzierzak, E.
BBSRC
1/01/20 → 31/12/22
Project: Research
Transfer of Adv Grant: DENOVOHSC
Dzierzak, E.
EU government bodies
1/01/15 → 31/12/19
Project: Research

Elaine Dzierzak
- Elaine.Dzierzak@ed.ac.uk
- Deanery of Clinical Sciences - Chair of Haematological Regeneration
- Centre for Inflammation Research
- Edinburgh Haematopoiesis Network
Person: Academic: Research Active

Cite this

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title = "Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells",

abstract = "Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single cell transcriptomics and functional analyses to connect HSC identity to specific gene expression.Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit and CD27 phenotypic parameters that associate specificmolecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.",

keywords = "AGM, CD27, Gata2, development, embryo, functional identity, hematopoietic stem cell, heterogeneity, intra-aortic hematopoietic clusters, single-cell transcriptome, transplantation",

author = "Vink, {Chris Sebastiaan} and Calero-Nieto, {Fernando Jose} and Xiaonan Wang and Antonio Maglitto and Mariani, {Samanta Antonella} and Wajid Jawaid and Berthold G{\"o}ttgens and Elaine Dzierzak",

year = "2020",

month = may,

day = "12",

doi = "10.1016/j.celrep.2020.107627",

language = "English",

volume = "31",

journal = "Cell Reports",

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Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells. / Vink, Chris Sebastiaan; Calero-Nieto, Fernando Jose; Wang, Xiaonan; Maglitto, Antonio; Mariani, Samanta Antonella; Jawaid, Wajid; Göttgens, Berthold; Dzierzak, Elaine.

In: Cell Reports, Vol. 31, No. 6, 107627, 12.05.2020.

Research output: Contribution to journal › Article › peer-review

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T1 - Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells

AU - Vink, Chris Sebastiaan

AU - Calero-Nieto, Fernando Jose

AU - Wang, Xiaonan

AU - Maglitto, Antonio

AU - Mariani, Samanta Antonella

AU - Jawaid, Wajid

AU - Göttgens, Berthold

AU - Dzierzak, Elaine

PY - 2020/5/12

Y1 - 2020/5/12

N2 - Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single cell transcriptomics and functional analyses to connect HSC identity to specific gene expression.Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit and CD27 phenotypic parameters that associate specificmolecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.

AB - Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single cell transcriptomics and functional analyses to connect HSC identity to specific gene expression.Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit and CD27 phenotypic parameters that associate specificmolecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.

KW - AGM

KW - CD27

KW - Gata2

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KW - embryo

KW - functional identity

KW - hematopoietic stem cell

KW - heterogeneity

KW - intra-aortic hematopoietic clusters

KW - single-cell transcriptome

KW - transplantation

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DO - 10.1016/j.celrep.2020.107627

M3 - Article

VL - 31

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

M1 - 107627

ER -

Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells

Abstract

Keywords

Access to Document

Single cell hematopoietic fate acquisition during embryonic development: To be a stem cell or not?

Transfer of Adv Grant: DENOVOHSC

Elaine Dzierzak

Cite this