Tumor suppressor gene Rb is required for self-renewal of spermatogonial stem cells in mice
Name
Hu-2013-Tumor suppressor gen.pdf
Size
874.95 KB
Format
Adobe PDF
Checksum (MD5)
52e3a3bcb43305a0426453a9f095cac1
Author(s)
Hu, Yueh-Chiang
de Rooij, Dirk G.
Page, David C
Date Issued
July 2013
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Hu, Y.-C., D. G. de Rooij, and D. C. Page. “Tumor Suppressor Gene Rb Is Required for Self-Renewal of Spermatogonial Stem Cells in Mice.” Proceedings of the National Academy of Sciences 110, no. 31 (July 30, 2013): 12685–12690.
Version
Final published version
Abstract
The retinoblastoma tumor suppressor gene Rb is essential for maintaining the quiescence and for regulating the differentiation of somatic stem cells. Inactivation of Rb in somatic stem cells typically leads to their overexpansion, often followed by increased apoptosis, defective terminal differentiation, and tumor formation. However, Rb’s roles in germ-line stem cells have not been explored. We conditionally disrupted the Rb gene in mouse germ cells in vivo and discovered unanticipated consequences for GFRa1-protein-expressing A[subscript single] (GFRa1[superscript +] A[subscript s]) spermatogonia, the major source of male germ-line stem cells. Rb-deficient GFRa1[superscript +] A[subscript s] spermatogonia were present at normal density in testes 5 d after birth, but they lacked the capacity for self-renewal, resulting in germ cell depletion by 2 mo of age. Rb deficiency did not affect the proliferative activity of GFRa1[superscript +] A[subscript s] spermatogonia, but their progeny were exclusively transit-amplifying progenitor spermatogonia and did not include GFRa1[superscript +] A[subscript s] spermatogonia. In addition, Rb deficiency caused prolonged proliferation of progenitor spermatogonia, transiently enlarging this population. Despite these defects, Rb deficiency did not block terminal differentiation into functional sperm; offspring were readily obtained from young males whose germ cell pool was not yet depleted. We conclude that Rb is required for self-renewal of germ-line stem cells, but contrary to its critical roles in somatic stem cells, it is dispensable for their proliferative activity and terminal differentiation. Thus, this study identifies an unexpected function for Rb in maintaining the stem cell pool in the male germ line.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1311548110
