Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter

Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter

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ABSTRACT Haematopoietic stem cells (HSCs) are the founder cells of the adult haematopoietic system, and thus knowledge of the molecular program directing their generation during development


is important for regenerative haematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus—the aorta,


vitelline and umbilical arteries, yolk sac and placenta1,2. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters3 and that Runx1


functions during the transition from ‘haemogenic endothelium’ to HSCs4,5. Here we show by conditional deletion that Runx1 activity in vascular-endothelial-cadherin-positive endothelial cells


is indeed essential for intra-arterial cluster, haematopoietic progenitor and HSC formation in mice. In contrast, Runx1 is not required in cells expressing Vav1, one of the first


pan-haematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for haematopoietic progenitor and HSC formation from the


vasculature, but its requirement ends once or before Vav is expressed. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution


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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS MAPPING HUMAN HAEMATOPOIETIC STEM CELLS FROM HAEMOGENIC ENDOTHELIUM TO


BIRTH Article 13 April 2022 HAEMATOPOIETIC STEM AND PROGENITOR CELL HETEROGENEITY IS INHERITED FROM THE EMBRYONIC ENDOTHELIUM Article Open access 17 July 2023 IDENTIFYING A NOVEL ROLE FOR


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assistance with flow, K. Downs for technical advice, T. Graf for the Vav-Cre mice, and P. Huber for the _Cdh5_ sequences. This work was supported by R01HL091724 (N.A.S.), R01DK54077 (E.D.)


and T32 AI-07519 (B.M.Z.). Core services were supported in part by the Norris Cotton Cancer Center (NIH CA23108) and the Abramson Family Cancer Research Institute. AUTHOR CONTRIBUTIONS T.Y.


performed the experiments in Fig. 3d. B.M.Z. performed the experiments in Fig. 1b, d. M.J.C. performed all the remaining experiments. E.D. participated in the interpretation of the


experiments and writing the manuscript. N.A.S. participated in the design and interpretation of the experiments, wrote the manuscript and made the figures. AUTHOR INFORMATION Author notes *


Michael J. Chen & Nancy A. Speck Present address: Present address: Abramson Family Cancer Research Institute and Department of Cell and Developmental Biology, University of Pennsylvania


School of Medicine, Philadelphia, Pennsylvania 19104, USA., AUTHORS AND AFFILIATIONS * Department of Biochemistry,, Michael J. Chen, Brandon M. Zeigler & Nancy A. Speck * Department of


Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA, Michael J. Chen * Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands


Tomomasa Yokomizo & Elaine Dzierzak Authors * Michael J. Chen View author publications You can also search for this author inPubMed Google Scholar * Tomomasa Yokomizo View author


publications You can also search for this author inPubMed Google Scholar * Brandon M. Zeigler View author publications You can also search for this author inPubMed Google Scholar * Elaine


Dzierzak View author publications You can also search for this author inPubMed Google Scholar * Nancy A. Speck View author publications You can also search for this author inPubMed Google


Scholar CORRESPONDING AUTHOR Correspondence to Nancy A. Speck. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains Supplementary Figures 1-2 with Legends and Supplementary


Tables 1-5 (PDF 754 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 RIGHTS AND PERMISSIONS Reprints and


permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Chen, M., Yokomizo, T., Zeigler, B. _et al._ Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter.


_Nature_ 457, 887–891 (2009). https://doi.org/10.1038/nature07619 Download citation * Received: 16 July 2008 * Accepted: 07 November 2008 * Published: 01 February 2009 * Issue Date: 12


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