BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.

Stem Cell Reports

Department of Cell Biology, Erasmus Medical Center, Erasmus MC Stem Cell Institute, 3000 CA Rotterdam, the Netherlands; Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Electronic address:

Published: March 2016

Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788785PMC
http://dx.doi.org/10.1016/j.stemcr.2016.01.016DOI Listing

Publication Analysis

Top Keywords

hematopoietic stem
8
stem cells
8
embryonic stages
8
hsc types
8
bmp hedgehog
4
hedgehog regulate
4
regulate distinct
4
agm
4
distinct agm
4
agm hematopoietic
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!