Featured Review: Genetic and Epigenetic Regulators of Pluripotency

Featured Review: Genetic and Epigenetic Regulators of Pluripotency
    For centuries, researchers throughout the world have been fascinated by the delicately orchestrated series of signaling events that manifest from the early totipotent zygote, early blastomere, and inner cell mass (ICM) to the complex differentiated organ structures and their intricately bound physiological systems that ultimately manifest the mature human body. During primary mammalian development, major epigenetic changes accompany the initial switch from totipotency to pluripotency that occurs during differentiation of the blastomere into the ICM and trophectoderm. Being ICM derived, these changes are particularly relevant to human embryonic stem cells (ESCs). These pluripotent cells have been the recent gold rush in cellular biology, yet we still have a very general understanding of how they maintain unlimited proliferation and self-renewal, in vitro.
    While ESCs have major implications for regenerative therapies, it is useful to recall that in-vitro modeling of human development, disease, and differentiation are simply one scientist’s best guess of how to most adequately recapitulate the delicate patterns of the naturally developing body so as to ascertain by testable hypothesis a plausible mechanistic signaling network responsible for their particular scientific question. In this case, it is therefore critical to recall, in-vivo, the pluripotent ESCs of the ICM, by their nature, must differentiate into all somatic cell types, and any other cue instructing otherwise would likely result in an early terminal fate. On the contrary, it is the unlimited proliferation and self-renewing pluripotent property of these progenitors that makes ESCs such an attractive candidate for creating an unlimited source of their transplantable differentiated counterparts. The very core of such long-term artificial propagation negates the inherent in-vivo developmental nature of these cells to differentiate into the human body.
    Therefore, to more accurately determine the basic mechanisms involved in human ESC self-renewal, so that we may manipulate these systems to our advantage, it is only fitting to start from the beginning, with an understanding of early mammalian development and the epigenetic changes that permit the initial signaling cascades responsible for primary differentiation. An excellent "Leading Edge" Review entitled Genetic and Epigenetic Regulators of Pluripotency by M. Azim Surani, Katsuhiko Hayashi, and Petra Hajkova published in the journal Cell details the early genetic and epigenetic mechanisms that regulate the early transitions from totipotency to pluripotency in the mouse blastocyst. In addition, it may be possible to manipulate and reprogram somatic derivatives into pluripotent counterparts as we continue to unravel the complex mechanisms that underlie early development. Check out this month’s StemCellCommunity, "Editor’s Choice."    - Dustin R Wakeman February 26, 2007
ARTICLE:Surani MA, Hayashi K, Hajkova P. Genetic and epigenetic regulators of pluripotency. Cell. 2007 Feb 23;128(4):747-62.