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Modeling mammalian spermatogonial differentiation and meiotic initiation in vitro

In mammalian testes, premeiotic spermatogonia respond to retinoic acid by completing an essential lengthy differentiation program before initiating meiosis. The molecular and cellular changes directing these developmental processes remain largely undefined. This wide gap in knowledge is due to two u...

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Detalles Bibliográficos
Autores principales: Kirsanov, Oleksandr, Johnson, Taylor, Malachowski, Taylor, Niedenberger, Bryan A., Gilbert, Emma A., Bhowmick, Debajit, Ozdinler, P. Hande, Gray, Douglas A., Fisher-Wellman, Kelsey, Hermann, Brian P., Geyer, Christopher B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845750/
https://www.ncbi.nlm.nih.gov/pubmed/36250451
http://dx.doi.org/10.1242/dev.200713
Descripción
Sumario:In mammalian testes, premeiotic spermatogonia respond to retinoic acid by completing an essential lengthy differentiation program before initiating meiosis. The molecular and cellular changes directing these developmental processes remain largely undefined. This wide gap in knowledge is due to two unresolved technical challenges: (1) lack of robust and reliable in vitro models to study differentiation and meiotic initiation; and (2) lack of methods to isolate large and pure populations of male germ cells at each stage of differentiation and at meiotic initiation. Here, we report a facile in vitro differentiation and meiotic initiation system that can be readily manipulated, including the use of chemical agents that cannot be safely administered to live animals. In addition, we present a transgenic mouse model enabling fluorescence-activated cell sorting-based isolation of millions of spermatogonia at specific developmental stages as well as meiotic spermatocytes.