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Hhex regulates murine lymphoid progenitor survival independently of Stat5 and Cdkn2a.

Authors
  • Jackson, Jacob T1
  • O'Donnell, Kristy2
  • Light, Amanda1
  • Goh, Wilford1
  • Huntington, Nicholas D1
  • Tarlinton, David M2
  • McCormack, Matthew P3
  • 1 Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. , (Australia)
  • 2 Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia. , (Australia)
  • 3 Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia. , (Australia)
Type
Published Article
Journal
European Journal of Immunology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 23, 2020
Identifiers
DOI: 10.1002/eji.201948371
PMID: 32090320
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The transcription factor Hhex (hematopoietically expressed homeobox gene) is critical for development of multiple lymphoid lineages beyond the common lymphoid progenitor. In addition, Hhex regulates hematopoietic stem cell (HSC) self-renewal, emergency hematopoiesis, and acute myeloid leukemia initiation and maintenance. Hhex mediates its effects on HSCs and acute myeloid leukemia stem cells via repression of the Cdkn2a tumor suppressor locus. However, we report here that loss of Cdkn2a does not rescue the failure of lymphoid development caused by loss of Hhex. As loss of Hhex causes apoptosis of lymphoid progenitors associated with impaired Bcl2 expression and defective Stat5b signaling, we tested the effects of rescuing these pathways using transgenic mice. Expression of the anti-apoptotic factor Bcl2, but not activated Stat5, rescued the development of T-, B-, and NK-cell lineages in the absence of Hhex. These results indicate that Bcl2 expression, but not Stat5b signaling or loss of Cdkn2a, can overcome the lymphoid deficiencies caused by the absence of Hhex, suggesting that the primary role of this transcription factor is to promote survival of lymphoid progenitors during early lymphoid development. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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