title: ID4 levels dictate the stem cell state in mouse spermatogonia.
abstract: Spermatogenesis is a classic model of cycling cell lineages that depend on a balance between stem cell self-renewal for continuity and the formation of progenitors as the initial step in the production of differentiated cells. The mechanisms that guide the continuum of spermatogonial stem cell (SSC) to progenitor spermatogonial transition and precise identifiers of subtypes in the process are undefined. Here we used anId4-eGfpreporter mouse to discover that EGFP intensity is predictive of the subsets, with the ID4-EGFPBrightpopulation being mostly, if not purely, SSCs, whereas the ID4-EGFPDimpopulation is in transition to the progenitor state. These subsets are also distinguishable by transcriptome signatures. Moreover, using a conditional overexpression mouse model, we found that transition from the stem cell to the immediate progenitor state requires downregulation ofId4coincident with a major change in the transcriptome. Collectively, our results demonstrate that the level of ID4 is predictive of stem cell or progenitor capacity in spermatogonia and dictates the interface of transition between the different functional states.
authors.affiliation: Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
authors.forename: Aileen R
authors.initials: AR
authors.lastname: Helsel
authors.affiliation: Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.|Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, QH 810001, China.
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Yang
authors.affiliation: Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
authors.forename: Melissa J
authors.identifier: 0000-0001-6692-4351
authors.initials: MJ
authors.lastname: Oatley
authors.affiliation: Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
authors.forename: Tessa
authors.initials: T
authors.lastname: Lord
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Fred
authors.initials: F
authors.lastname: Sablitzky
authors.affiliation: Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA joatley@vetmed.wsu.edu.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Oatley
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013091:Spermatogenesis; D013093:Spermatogonia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D013737:Testis / Q000378:metabolism; D059467:Transcriptome; D019076:Transgenes
chemical_list: C086479:Idb4 protein, mouse; D051796:Inhibitor of Differentiation Proteins; D049452:Green Fluorescent Proteins
keywords: ID4; Progenitor; Spermatogonia; Stem cell