Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function.

Abstract:

:Hematopoiesis is a tightly regulated process resulting in the production of blood cells. Self-renewal and differentiation of hematopoietic stem cells (HSCs) are key processes in hematopoietic development. Disruption of these steps can lead to altered cell distribution and disease. To investigate the role of the nuclear factor-κB subunit RelA/p65 in the regulation of HSCs in vivo, we generated mice lacking RelA/p65 in the hematopoietic compartment. Using this model system, we show that loss of p65 severely impairs HSC function and occurs in conjunction with increased hematopoietic stem and progenitor cell cycling, extramedullary hematopoiesis, and differentiation defects. Gene array studies of phenotypic HSCs indicate the up-regulation of genes normally expressed in lineage restricted cells, as well as the down-regulation of genes involved in HSC maintenance and homeostasis. We hypothesize that changes in gene expression in p65-deficient cells lead to decreased self-renewal and differentiation efficiency of hematopoietic stem and progenitor cells. These studies demonstrate that p65 is an important regulator of hematopoiesis through the transcription of genes involved in HSC fate.

journal_name

Blood

journal_title

Blood

authors

Stein SJ,Baldwin AS

doi

10.1182/blood-2013-02-486142

subject

Has Abstract

pub_date

2013-06-20 00:00:00

pages

5015-24

issue

25

eissn

0006-4971

issn

1528-0020

pii

blood-2013-02-486142

journal_volume

121

pub_type

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