title: Functional and molecular features of the Id4+ germline stem cell population in mouse testes.
abstract: The maintenance of cycling cell lineages relies on undifferentiated subpopulations consisting of stem and progenitor pools. Features that delineate these cell types are undefined for many lineages, including spermatogenesis, which is supported by an undifferentiated spermatogonial population. Here, we generated a transgenic mouse line in which spermatogonial stem cells are marked by expression of an inhibitor of differentiation 4 (Id4)-green fluorescent protein (Gfp) transgene. We found that Id4-Gfp(+) cells exist primarily as a subset of the type A(single) pool, and their frequency is greatest in neonatal development and then decreases in proportion during establishment of the spermatogenic lineage, eventually comprising ∼ 2% of the undifferentiated spermatogonial population in adulthood. RNA sequencing analysis revealed that expression of 11 and 25 genes is unique for the Id4-Gfp(+)/stem cell and Id4-Gfp(-)/progenitor fractions, respectively. Collectively, these findings provide the first definitive evidence that stem cells exist as a rare subset of the A(single) pool and reveal transcriptome features distinguishing stem cell and progenitor states within the mammalian male germline.
authors.affiliation: School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, USA;
authors.forename: Frieda
authors.initials: F
authors.lastname: Chan
authors.affiliation: School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, USA;
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Oatley
authors.affiliation: School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, USA;
authors.forename: Amy V
authors.initials: AV
authors.lastname: Kaucher
authors.affiliation: School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, USA;
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, University of Maryland at Baltimore County, Baltimore, Maryland 21250, USA;
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Bieberich
authors.affiliation: Department of Animal Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Cooduvalli S
authors.initials: CS
authors.lastname: Shashikant
authors.affiliation: School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, USA;
authors.forename: Jon M
authors.initials: JM
authors.lastname: Oatley
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: C086479:Idb4 protein, mouse; D051796:Inhibitor of Differentiation Proteins; D049452:Green Fluorescent Proteins
keywords: Id4; germline stem cell; spermatogonia; spermatogonial stem cell; transcriptome