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DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment
Teng Zhang1, Jon Oatley2, Vivian J Bardwell1,3
1Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
Plos Genetics
|September 2, 2016
Summary
Doublesex- and mab-3-related transcription factor 1 (Dmrt1) maintains mouse spermatogonial stem cells (SSCs) under normal conditions and enables progenitor cells to restore the SSC pool after depletion, ensuring robust sperm production.
Area of Science:
- Reproductive biology
- Developmental biology
- Stem cell research
Background:
- Male mammals require a stable germ line stem cell system for continuous sperm production.
- Dmrt1 is a known regulator of male sexual differentiation.
- The role of Dmrt1 in spermatogonial stem cell (SSC) homeostasis is not fully understood.
Purpose of the Study:
- To investigate the function of Dmrt1 in maintaining mouse spermatogonial stem cell (SSC) homeostasis.
- To determine Dmrt1's role in SSC self-renewal and differentiation.
- To elucidate Dmrt1's involvement in spermatogenesis recovery after germ cell depletion.
Main Methods:
- Investigated Dmrt1's role in mouse SSC homeostasis using genetic manipulation.
- Analyzed gene expression, including Plzf and Ngn3, in relation to Dmrt1.
- Utilized busulfan treatment to induce germ cell depletion and assess spermatogenesis recovery.
- Employed Id4-Gfp transgene to mark SSCs.
Main Results:
- Dmrt1 maintains SSCs during steady-state spermatogenesis by regulating Plzf expression.
- Dmrt1 is essential for the recovery of spermatogenesis following germ cell depletion.
- Dmrt1 enables committed progenitor cells (Ngn3-positive) to repopulate the SSC pool after busulfan-induced depletion.
Conclusions:
- Dmrt1 plays a dual role in SSC maintenance: preserving the stem cell pool normally and facilitating its restoration by progenitor cells after injury.
- Dmrt1 is critical for the resilience and recovery of the male germ line stem cell system.
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