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

Access to Document

10.1038/ncomms3924

Cite this

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",

issn = "2041-1723",

publisher = "Springer",

}

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

Access to Document

Fingerprint

Cite this