Functionally redundant roles of ID family proteins in spermatogonial stem cells.

Autor:	La HM; Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia; University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, VIC 3000, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia., Chan AL; Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia., Hutchinson AM; Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia., Su BYM; Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia., Rossello FJ; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC 3052, Australia; Novo Nordisk Foundation Center for Stem Cell Medicine, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC 3800, Australia., Schittenhelm RB; Monash Proteomics & Metabolomics Platform, Monash Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia., Hobbs RM; Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia. Electronic address: robin.hobbs@monash.edu.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2024 Oct 08; Vol. 19 (10), pp. 1379-1388. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.1016/j.stemcr.2024.08.011
Abstrakt:	Spermatogonial stem cells (SSCs) are essential for sustained sperm production, but SSC regulatory mechanisms and markers remain poorly defined. Studies have suggested that the Id family transcriptional regulator Id4 is expressed in SSCs and involved in SSC maintenance. Here, we used reporter and knockout models to define the expression and function of Id4 in the adult male germline. Within the spermatogonial pool, Id4 reporter expression and inhibitor of DNA-binding 4 (ID4) protein are found throughout the GFRα1+ fraction, comprising the self-renewing population. However, Id4 deletion is tolerated by adult SSCs while revealing roles in meiotic spermatocytes. Cultures of undifferentiated spermatogonia could be established following Id4 deletion. Importantly, ID4 loss in undifferentiated spermatogonia triggers ID3 upregulation, and both ID proteins associate with transcription factor partner TCF3 in wild-type cells. Combined inhibition of IDs in cultured spermatogonia disrupts the stem cell state and blocks proliferation. Our data therefore demonstrate critical but functionally redundant roles of IDs in SSC function. Competing Interests: Declaration of interests F.J.R. receives institutional support as a co-investigator and is subcontracted by Peter MacCallum Cancer Centre for an investigator-initiated trial, which receives funding from Sanofi/Regeneron Pharmaceuticals. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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