Biomedical Engineering Reference
In-Depth Information
Chapter 7
Molecular Mechanisms Regulating
Spermatogonial Stem Cell Fate Decisions
Olga M. Ocón-Grove and Jon M. Oatley
Abstract
Spermatogenesis in the mammalian testis is a classic stem cell dependent
process relying on spermatogonial stem cells (SSCs) to undergo two distinct fate
decisions referred to as self-renewal and differentiation. Deciphering the mecha-
nisms that control these functions is crucial to understanding spermatogenesis and
can provide insight into the biology of tissue-specific stem cells. In general SSC
fate decisions are controlled extrinsically from influences of a niche microenvi-
ronment and internally by regulation of specific molecular pathways. In mice, the
growth factor glial cell line-derived neurotrophic (GDNF) functions as an essential
extrinsic stimulator of SSC self-renewal and survival by activating SRC family
kinase, phosphoinositide-3-kinase/AKT, and RAS signaling pathways. Other known
extrinsic stimulators of SSC self-renewal include fibroblast growth factor 2 and
colony stimulating factor 1. Internally, expression of specific transcription regula-
tors including
Bcl6b
,
Etv5
, and
Lhx1
are regulated by GDNF and these play roles in
regulating SSC self-renewal and survival. Additionally, other non GDNF-regulated
genes including
Mili, Ngn3, Nanos2, Oct3/4, and Taf4b
have also been implicated
as regulators of SSC fate decisions.
Keywords
Spermatogonial stem cell • Niche • Self-renewal • Signaling
• Transcription factor
J.M. Oatley (
*
)
Department of Dairy and Animal Science, Center for Reproductive Biology and Health,
College of Agricultural Sciences, The Pennsylvania State University, University Park,
PA 16802, USA
e-mail: jmo15@psu.edu
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