TY - JOUR
T1 - Identification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling
AU - Mascarenhas, MI
AU - Parker, A
AU - Dzierzak, Elaine
AU - Ottersbach, K (Katrin)
PY - 2009
Y1 - 2009
N2 - The first adult-repopulating hematopoietic stem cells (HSCs) are detected starting at day 10.5 of gestation in the aorta-gonads-mesonephros ( AGM) region of the mouse embryo. Despite the importance of the AGM in initiating HSC production, very little is currently known about the regulators that control HSC emergence in this region. We have therefore further defined the location of HSCs in the AGM and incorporated this information into a spatial and temporal comparative gene expression analysis of the AGM. The comparisons included gene expression profiling ( 1) in the newly identified HSC-containing region compared with the region devoid of HSCs, ( 2) before and after HSC emergence in the AGM microenvironment, and ( 3) on populations enriched for HSCs and their putative precursors. Two genes found to be up-regulated at the time and place where HSCs are first detected, the cyclin-dependent kinase inhibitor p57Kip2/Cdkn1c and the insulin-like growth factor 2, were chosen for further analysis. We demonstrate here that they play a novel role in AGM hematopoiesis. Interestingly, many genes involved in the development of the tissues surrounding the dorsal aorta are also upregulated during HSC emergence, suggesting that the regulation of HSC generation occurs in coordination with the development of other organs. ( Blood. 2009; 114: 4645-4653)
AB - The first adult-repopulating hematopoietic stem cells (HSCs) are detected starting at day 10.5 of gestation in the aorta-gonads-mesonephros ( AGM) region of the mouse embryo. Despite the importance of the AGM in initiating HSC production, very little is currently known about the regulators that control HSC emergence in this region. We have therefore further defined the location of HSCs in the AGM and incorporated this information into a spatial and temporal comparative gene expression analysis of the AGM. The comparisons included gene expression profiling ( 1) in the newly identified HSC-containing region compared with the region devoid of HSCs, ( 2) before and after HSC emergence in the AGM microenvironment, and ( 3) on populations enriched for HSCs and their putative precursors. Two genes found to be up-regulated at the time and place where HSCs are first detected, the cyclin-dependent kinase inhibitor p57Kip2/Cdkn1c and the insulin-like growth factor 2, were chosen for further analysis. We demonstrate here that they play a novel role in AGM hematopoiesis. Interestingly, many genes involved in the development of the tissues surrounding the dorsal aorta are also upregulated during HSC emergence, suggesting that the regulation of HSC generation occurs in coordination with the development of other organs. ( Blood. 2009; 114: 4645-4653)
U2 - 10.1182/blood-2009-06-230037
DO - 10.1182/blood-2009-06-230037
M3 - Article
C2 - 19794138
SN - 0006-4971
VL - 114
SP - 4645
EP - 4653
JO - Blood
JF - Blood
IS - 21
ER -