Functionally redundant roles of ID family proteins in spermatogonial stem cells
Files
(Published version)
Date
2024
Authors
La, H.M.
Chan, A.-L.
Hutchinson, A.M.
Su, B.Y.M.
Rossello, F.J.
Schittenhelm, R.B.
Hobbs, R.M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Stem Cell Reports, 2024; 19(10):1379-1388
Statement of Responsibility
Hue M. La, Ai-Leen Chan, Ashlee M. Hutchinson, Bianka Y.M. Su, Fernando J. Rossello, Ralf B. Schittenhelm, and Robin M. Hobbs
Conference Name
Abstract
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 GFRa1+ 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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2024 The Author(s). Published by Elsevier Inc. on behalf of International Society for Stem Cell Research. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).