2 research outputs found
The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression
Apoptosis is an essential process in embryonic tissue remodeling and adult
tissue homeostasis. Within the adult hematopoietic system, it allows for
tight regulation of hematopoietic cell subsets. Previously, it was shown
that B-cell leukemia 2 (Bcl-2) overexpression in the adult increases the
viability and activity of hematopoietic cells under normal and/or
stressful conditions. However, a role for apoptosis in the embryonic
hematopoietic system has not yet been established. Since the first
hematopoietic stem cells (HSCs) are generated within the
aortagonad-mesonephros (AGM; an actively remodeling tissue) region
beginning at embryonic day 10.5, we examined this tissue for expression of
apoptosis-related genes and ongoing apoptosis. Here, we show expression of
several proapoptotic and antiapoptotic genes in the AGM. We also generated
transgenic mice overexpressing Bcl-2 under the control of the
transcriptional regulatory elements of the HSC marker stem cell antigen-1
(Sca-1), to test for the role of cell survival in the regulation of AGM
HSCs. We provide evidence for increased numbers and viability of Sca-1(+)
cells in the AGM and subdissected midgestation aortas, the site where HSCs
are localized. Most important, our in vivo transplantation data show that
Bcl-2 overexpression increases AGM and fetal liver HSC activity, strongly
suggesting that apoptosis plays a role in HSC development