Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Gemma Swiers; Claudia Baumann; John O'Rourke; Eleni Giannoulatou; Stephen Taylor; Anagha Joshi; Victoria Moignard; Cristina Pina; Thomas Bee; Konstantinos D Kokkaliaris; Momoko Yoshimoto; Mervin C Yoder; Jonathan Frampton; Timm Schroeder; Tariq Enver; Berthold Göttgens; Marella F T R de Bruijn

doi:10.1038/ncomms3924

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Gemma Swiers, Claudia Baumann, John O'Rourke, Eleni Giannoulatou, Stephen Taylor, Anagha Joshi, Victoria Moignard, Cristina Pina, Thomas Bee, Konstantinos D Kokkaliaris, Momoko Yoshimoto, Mervin C Yoder, Jonathan Frampton, Timm Schroeder, Tariq Enver, Berthold Göttgens, Marella F T R de Bruijn

Cancer and Genomic Sciences

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

109 Citations (Scopus)

Abstract

Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Original language	English
Pages (from-to)	2924
Journal	Nature Communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3924
Publication status	Published - 2013

Keywords

Animals
Core Binding Factor Alpha 2 Subunit
Embryo, Mammalian
Enhancer Elements, Genetic
Female
Gene Expression Regulation, Developmental
Green Fluorescent Proteins
Hemangioblasts
Male
Mice
Mice, Transgenic
Pregnancy
Single-Cell Analysis

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10.1038/ncomms3924

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Swiers, G., Baumann, C., O'Rourke, J., Giannoulatou, E., Taylor, S., Joshi, A., Moignard, V., Pina, C., Bee, T., Kokkaliaris, K. D., Yoshimoto, M., Yoder, M. C., Frampton, J., Schroeder, T., Enver, T., Göttgens, B., & de Bruijn, M. F. T. R. (2013). Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level. Nature Communications, 4, 2924. https://doi.org/10.1038/ncomms3924

@article{24c158cfceca4d8b957c289481d07cba,

title = "Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level",

abstract = "Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.",

keywords = "Animals, Core Binding Factor Alpha 2 Subunit, Embryo, Mammalian, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Hemangioblasts, Male, Mice, Mice, Transgenic, Pregnancy, Single-Cell Analysis",

author = "Gemma Swiers and Claudia Baumann and John O'Rourke and Eleni Giannoulatou and Stephen Taylor and Anagha Joshi and Victoria Moignard and Cristina Pina and Thomas Bee and Kokkaliaris, {Konstantinos D} and Momoko Yoshimoto and Yoder, {Mervin C} and Jonathan Frampton and Timm Schroeder and Tariq Enver and Berthold G{\"o}ttgens and {de Bruijn}, {Marella F T R}",

year = "2013",

doi = "10.1038/ncomms3924",

language = "English",

volume = "4",

pages = "2924",

journal = "Nature Communications",

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Swiers, G, Baumann, C, O'Rourke, J, Giannoulatou, E, Taylor, S, Joshi, A, Moignard, V, Pina, C, Bee, T, Kokkaliaris, KD, Yoshimoto, M, Yoder, MC, Frampton, J, Schroeder, T, Enver, T, Göttgens, B & de Bruijn, MFTR 2013, 'Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level', Nature Communications, vol. 4, pp. 2924. https://doi.org/10.1038/ncomms3924

TY - JOUR

T1 - Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

AU - Swiers, Gemma

AU - Baumann, Claudia

AU - O'Rourke, John

AU - Giannoulatou, Eleni

AU - Taylor, Stephen

AU - Joshi, Anagha

AU - Moignard, Victoria

AU - Pina, Cristina

AU - Bee, Thomas

AU - Kokkaliaris, Konstantinos D

AU - Yoshimoto, Momoko

AU - Yoder, Mervin C

AU - Frampton, Jonathan

AU - Schroeder, Timm

AU - Enver, Tariq

AU - Göttgens, Berthold

AU - de Bruijn, Marella F T R

PY - 2013

Y1 - 2013

N2 - Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

AB - Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

KW - Animals

KW - Core Binding Factor Alpha 2 Subunit

KW - Embryo, Mammalian

KW - Enhancer Elements, Genetic

KW - Female

KW - Gene Expression Regulation, Developmental

KW - Green Fluorescent Proteins

KW - Hemangioblasts

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Pregnancy

KW - Single-Cell Analysis

U2 - 10.1038/ncomms3924

DO - 10.1038/ncomms3924

M3 - Article

C2 - 24326267

SN - 2041-1723

VL - 4

SP - 2924

JO - Nature Communications

JF - Nature Communications

ER -

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Abstract

Keywords

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