Functional identification of the hematopoietic stem cell niche in the ventral domain of the embryonic dorsal aorta

doi:10.1073/pnas.0700984104

Functional identification of the hematopoietic stem cell niche in the ventral domain of the embryonic dorsal aorta

Samir Taoudi and
Alexander Medvinsky*

Ontogeny of Haematopoietic Stem Cells Group, Medical Research Council/Juvenile Diabetes Research Foundation Centre for Development in Stem Cell Biology, Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH9 3JQ, United Kingdom

Edited by Stuart H. Orkin, Harvard Medical School, Boston, MA, and approved March 28, 2007 (received for review February 6, 2007)

Abstract

The first definitive/adult-type hematopoietic stem cells (HSCs) in the mouse aorta–gonad–mesonephros region emerge between embryonic days 10.5 and 11.5. The discovery of clusters of hematopoietic cells on the ventral luminal surface of the dorsal aorta in various vertebrate species has led to speculation that the floor of the dorsal aorta may play an essential role for the development of the definitive hematopoietic system. Here, we functionally show affiliation of definitive HSCs with the ventral floor of the dorsal aorta, whereas colony-forming hematopoietic activity is associated with both ventral and dorsal domains. We show that a rare population of PECAM1^highCD45⁺ cells, within which definitive HSCs reside, is predominantly localized to intraaortic clusters. Furthermore, using ex vivo culture analysis, we demonstrate that the ventral domain of the dorsal aorta has an exclusive functional capacity of inducing and expanding definitive HSCs.

Footnotes

*To whom correspondence should be addressed at:
Institute for Stem Cell Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JQ, United Kingdom.
E-mail: a.medvinsky{at}ed.ac.uk
Author contributions: S.T. and A.M. designed research; S.T. performed research; S.T. analyzed data; and S.T. and A.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700984104/DC1.
Abbreviations:

AGM region,

aorta-gonad-mesonephros region;

Ao,

dorsal aorta;

AoD,

dorsal domain of the Ao;

AoV,

ventral domain of the Ao.