Extracellular matrix signaling activates differentiation of adult ovary-derived oogonial stem cells in a species-specific manner
Article In Press
Julie A. MacDonald, B.S.a, Yasushi Takai, M.D., Ph.D.b, Osamu Ishihara, M.D., Ph.D.b, Hiroyuki Seki, M.D., Ph.D.b, Dori C. Woods, Ph.D.a, Jonathan L. Tilly, Ph.D.
To test if ovarian microenvironmental cues affect oogonial stem cell (OSC) function in a species-specific manner.
Animal and human study.
Human ovarian cells obtained from cryopreserved ovarian cortical tissue of reproductive-age women, and ovarian cells and tissues from female C57BL/6 mice.
Mouse ovarian tissue, mouse OSCs (mOSCs) and human OSCs (hOSCs) were analyzed for extracellular matrix (ECM) protein expression, and OSCs isolated from adult mouse and human ovaries were cultured in the absence or presence of ECM proteins without or with an integrin signaling inhibitor.
Main Outcome Measure(s)
Gene expression and in vitro derived (IVD) oocyte formation.
Culture of mOSCs on a collagen-based ECM significantly elevated the rate of differentiation of the cells into IVD oocytes. Mouse OSCs expressed many integrins, including Arg-Gly-Asp (RGD)–binding subunits, and ECM-mediated increases in mOSC differentiation were blocked by addition of integrin-antagonizing RGD peptides. In comparison, hOSCs expressed a different pattern of integrin subunits compared with mOSCs, and hOSCs were unresponsive to a collagen-based ECM; however, hOSCs exhibited increased differentiation into IVD oocytes when cultured on laminin.
These data, along with in silico analysis of ECM protein profiles in human ovaries, indicate that ovarian ECM-based niche components function in a species-specific manner to control OSC differentiation.