Journal article
MicroRNAs 221 and 222 regulate the undifferentiated state in mammalian male germ cells
Development (Cambridge), Vol.140(2), pp.280-290
01/15/2013
Handle:
https://hdl.handle.net/2376/117652
PMCID: PMC3597206
PMID: 23221369
Abstract
Continuity of cycling cell lineages relies on the activities of undifferentiated stem cell-containing subpopulations. Transition to a differentiating state must occur periodically in a fraction of the population to supply mature cells, coincident with maintenance of the undifferentiated state in others to sustain a foundational stem cell pool. At present, molecular mechanisms regulating these activities are poorly defined for most cell lineages. Spermatogenesis is a model process that is supported by an undifferentiated spermatogonial population and transition to a differentiating state involves attained expression of the KIT receptor. We found that impaired function of the X chromosome-clustered microRNAs 221 and 222 (miR-221/222) in mouse undifferentiated spermatogonia induces transition from a KIT
–
to a KIT
+
state and loss of stem cell capacity to regenerate spermatogenesis. Both
Kit
mRNA and KIT protein abundance are influenced by miR-221/222 function in spermatogonia. Growth factors that promote maintenance of undifferentiated spermatogonia upregulate miR-221/222 expression; whereas exposure to retinoic acid, an inducer of spermatogonial differentiation, downregulates miR-221/222 abundance. Furthermore, undifferentiated spermatogonia overexpressing miR-221/222 are resistant to retinoic acid-induced transition to a KIT
+
state and are incapable of differentiation
in vivo
. These findings indicate that miR-221/222 plays a crucial role in maintaining the undifferentiated state of mammalian spermatogonia through repression of KIT expression.
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Details
- Title
- MicroRNAs 221 and 222 regulate the undifferentiated state in mammalian male germ cells
- Creators
- Qi-En Yang - School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USAKaren E Racicot - Center for Reproductive Biology and Health, Department of Animal Sciences, Pennsylvania State University, University Park, PA 16802, USAAmy V Kaucher - School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USAMelissa J Oatley - School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USAJon M Oatley - School of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA
- Publication Details
- Development (Cambridge), Vol.140(2), pp.280-290
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- Company of Biologists
- Identifiers
- 99900547826501842
- Language
- English
- Resource Type
- Journal article