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Functionally redundant roles of ID family proteins in spermatogonial stem cells

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dc.contributor.authorLa, H.M.
dc.contributor.authorChan, A.-L.
dc.contributor.authorHutchinson, A.M.
dc.contributor.authorSu, B.Y.M.
dc.contributor.authorRossello, F.J.
dc.contributor.authorSchittenhelm, R.B.
dc.contributor.authorHobbs, R.M.
dc.date.issued2024
dc.description.abstractSpermatogonial 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.
dc.description.statementofresponsibilityHue M. La, Ai-Leen Chan, Ashlee M. Hutchinson, Bianka Y.M. Su, Fernando J. Rossello, Ralf B. Schittenhelm, and Robin M. Hobbs
dc.identifier.citationStem Cell Reports, 2024; 19(10):1379-1388
dc.identifier.doi10.1016/j.stemcr.2024.08.011
dc.identifier.issn2213-6711
dc.identifier.issn2213-6711
dc.identifier.orcidHobbs, R.M. [0000-0002-3853-2614]
dc.identifier.urihttps://hdl.handle.net/2440/147643
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1164019
dc.relation.granthttp://purl.org/au-research/grants/arc/DP220103555
dc.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/).
dc.source.urihttps://doi.org/10.1016/j.stemcr.2024.08.011
dc.subjectspermatogonial stem cells; germline; transcription factors; ID genes
dc.subject.meshSpermatocytes
dc.subject.meshSpermatogonia
dc.subject.meshCells, Cultured
dc.subject.meshStem Cells
dc.subject.meshAnimals
dc.subject.meshMice, Knockout
dc.subject.meshMice
dc.subject.meshCell Differentiation
dc.subject.meshSpermatogenesis
dc.subject.meshCell Proliferation
dc.subject.meshMale
dc.subject.meshGlial Cell Line-Derived Neurotrophic Factor Receptors
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors
dc.subject.meshInhibitor of Differentiation Proteins
dc.subject.meshTranscription Factor 3
dc.subject.meshAdult Germline Stem Cells
dc.titleFunctionally redundant roles of ID family proteins in spermatogonial stem cells
dc.typeJournal article
pubs.publication-statusPublished

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