The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Orelio C,Harvey KN,Miles C,Oostendorp RA,van der Horn K,Dzierzak E

doi

10.1182/blood-2003-06-1827

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

4084-92

issue

11

eissn

0006-4971

issn

1528-0020

pii

2003-06-1827

journal_volume

103

pub_type

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