Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells

Although ovarian theca cells play an indispensable role in folliculogenesis by providing follicular structural integrity and steroid substrates for estrogen production, little information is available about their recruitment, growth, and differentiation because their immature forms have not been ide...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 30; pp. 12389 - 12394
Main Authors:	Honda, Arata, Hirose, Michiko, Hara, Kenshiro, Matoba, Shogo, Inoue, Kimiko, Miki, Himomi, Hiura, Hitoshi, Kanatsu-Shinohara, Mito, Kanai, Yoshiakira, Kono, Tomohiro, Shinohara, Takashi, Ogura, Atsuo
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 24-07-2007 National Acad Sciences
Subjects:	Animals Animals, Newborn Biological Sciences Cell culture Cell Differentiation Cell growth Cell lines Cell Separation - methods Cells, Cultured Cellular biology Cultured cells Cytoplasm - metabolism Female Follicles Gene expression Gene Expression Regulation, Developmental Granulosa cells Lipid Metabolism Mice Microscopy, Electron, Transmission Oocytes Ovaries Stem Cell Transplantation Stem cells Stem Cells - cytology Stem Cells - metabolism Theca cells Theca Cells - cytology Theca Cells - metabolism Theca Cells - transplantation Transplantation Transplantation, Homologous
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Summary:	Although ovarian theca cells play an indispensable role in folliculogenesis by providing follicular structural integrity and steroid substrates for estrogen production, little information is available about their recruitment, growth, and differentiation because their immature forms have not been identified. We have isolated putative thecal stem cells with the ability to self-renew and differentiate in vivo and in vitro. They are similar to fibroblasts in morphology and proliferate in vitro as round colonies with a homogenous cell population. They were induced to differentiate into early precursors and steroidogenic cells in a stepwise manner after treatment with serum, luteinizing hormone, and paracrine factors from granulosa cells. At each differentiation step, these cells displayed appropriate gene expression and morphological markers and later secreted androstenedione. The fully mature morphology was achieved by coculture with isolated granulosa cells. When transplanted into the ovaries, the putative thecal stem cells colonized exclusively in the ovarian interstitium and the thecal layer of follicles as differentiated cells. Thus, thecal stem cells appear to be present in neonatal ovaries and can be isolated, purified, and induced to differentiate in vitro. Thecal stem cells could provide an invaluable in vitro experimental system to study interactions among the oocytes, granulosa cells, and theca cells during normal folliculogenesis and to study ovarian pathology caused by theca cell dysfunction.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Edited by R. Michael Roberts, University of Missouri, Columbia, MO, and approved June 7, 2007 Author contributions: A.H., M.H., T.K., and A.O. designed research; A.H., M.H., K.H., S.M., K.I., H.M., H.H., M.K.-S., Y.K., T.K., T.S., and A.O. performed research; M.K.-S. and T.S. contributed new reagents/analytic tools; A.H., M.H., K.H., S.M., K.I., and Y.K. analyzed data; and A.H., Y.K., and A.O. wrote the paper.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0703787104