title: DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment.
abstract: Male mammals produce sperm for most of postnatal life and therefore require a robust germ line stem cell system, with precise balance between self-renewal and differentiation. Prior work established doublesex- and mab-3-related transcription factor 1 (Dmrt1) as a conserved transcriptional regulator of male sexual differentiation. Here we investigate the role of Dmrt1 in mouse spermatogonial stem cell (SSC) homeostasis. We find that Dmrt1 maintains SSCs during steady state spermatogenesis, where it regulates expression of Plzf, another transcription factor required for SSC maintenance. We also find that Dmrt1 is required for recovery of spermatogenesis after germ cell depletion. Committed progenitor cells expressing Ngn3 normally do not contribute to SSCs marked by the Id4-Gfp transgene, but do so when spermatogonia are chemically depleted using busulfan. Removal of Dmrt1 from Ngn3-positive germ cells blocks the replenishment of Id4-GFP-positive SSCs and recovery of spermatogenesis after busulfan treatment. Our data therefore reveal that Dmrt1 supports SSC maintenance in two ways: allowing SSCs to remain in the stem cell pool under normal conditions; and enabling progenitor cells to help restore the stem cell pool after germ cell depletion.
authors: Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Teng
authors: T
authors: Zhang
authors: School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
authors: Jon
authors: J
authors: Oatley
authors: Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.|University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, United States of America.
authors: Vivian J
authors: VJ
authors: Bardwell
authors: Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.|University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, United States of America.
authors: David
authors: D
authors: Zarkower
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051796:Inhibitor of Differentiation Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; C110547:DMRT1 protein; C086479:Idb4 protein, mouse; C407737:Neurog3 protein, mouse; C513267:Zbtb16 protein, mouse