The Architectural Organization of Human Stem Cell Cycle Regulatory Machinery

Gary S. Stein, Janet L. Stein, Andre van J. Wijnen, Jane B. Lian, Martin Montecino, Ricardo      Medina, Kristie Kapinas, Prachi Ghule, Rodrigo Grandy, Sayyed K. Zaidi, Klaus A. Becker

doi:10.2174/138161212799859639

Abstract

Two striking features of human embryonic stem cells that support biological activity are an abbreviated cell cycle and reduced complexity to nuclear organization. The potential implications for rapid proliferation of human embryonic stem cells within the context of sustaining pluripotency, suppressing phenotypic gene expression and linkage to simplicity in the architectural compartmentalization of regulatory machinery in nuclear microenvironments is explored. Characterization of the molecular and architectural commitment steps that license human embryonic stem cells to initiate histone gene expression is providing understanding of the principal regulatory mechanisms that control the G1/S phase transition in primitive pluripotent cells. From both fundamental regulatory and clinical perspectives, further understanding of the pluripotent cell cycle in relation to compartmentalization of regulatory machinery in nuclear microenvironments is relevant to applications of stem cells for regenerative medicine and new dimensions to therapy where traditional drug discovery strategies have been minimally effective.

Keywords: Human embryonic stem cells, reprogrammed pluripotent cells, histone gene expression, nuclear organization, chromatin structure, microenvironments, G1/S phase transition, mitosis, Histone Locus Bodies (HLBs), Endocrinology