Stem Cells and Regenerative Medicine

StemCells280-220Human embryonic stem cells (hESCs) have a tremendous potential to be used for both therapeutic applications as well as for understanding basic biological processes. The potential to differentiate into any cell lineage and potential for unlimited cell division are unique characteristics of hESCs. We have discovered that this unlimited proliferative potential is linked to an abbreviated cell cycle; the embryonic stem cells have a shortened G1 phase of the cell cycle. This finding provides a paradigm to further explore cell growth regulatory mechanisms in the physiological context of pluripotency (see Cell Cycle, Cancer and Aging). Currently, we are examining mechanisms that mediate lengthening of the cell cycle and early stage of cell fate determination as pluripotent stem cells undergo differentiation.

In addition, we are examining osteogenic differentiation from mesenchymal stem cells to define the molecular basis of skeletal regenerative medicine (see Musculoskeletal Biology and Pathology).

Landmark Papers

  • Becker KA, Ghule PN, Lian JB, Stein JL, van Wijnen AJ, Stein GS. Cyclin D2 and the CDK substrate p220(NPAT) are required for self-renewal of human embryonic stem cells. J Cell Physiol. 2010 Feb;222(2):456-64.

  • Becker KA, Stein JL, Lian JB, van Wijnen AJ, Stein GS. Human embryonic stem cells are pre-mitotically committed to self-renewal and acquire a lengthened G1 phase upon lineage programming. J Cell Physiol. 2010 Jan;222(1):103-10.

  • Filion TM, Qiao M, Ghule PN, Mandeville M, van Wijnen AJ, Stein JL, Lian JB, Altieri DC, Stein GS. Survival responses of human embryonic stem cells to DNA damage. J Cell Physiol. 2009 Sep;220(3):586-92.

  • Xie R, Medina R, Zhang Y, Hussain S, Colby J, Ghule P, Sundararajan S, Keeler M, Liu LJ, van der Deen M, Mitra P, Lian JB, Rivera-Perez JA, Jones SN, Stein JL, van Wijnen AJ, Stein GS. The histone gene activator HINFP is a nonredundant cyclin E/CDK2 effector during early embryonic cell cycles. Proc Natl Acad Sci USA. 2009 Jul 28;106(30):12359-64.

  • Ghule PN, Dominski Z, Lian JB, Stein JL, van Wijnen AJ, Stein GS. The subnuclear organization of histone gene regulatory proteins and 3′ end processing factors of normal somatic and embryonic stem cells is compromised in selected human cancer cell types. J Cell Physiol. 2009 Jul;220(1):129-35.

  • Ghule PN, Dominski Z, Yang XC, Marzluff WF, Becker KA, Harper JW, Lian JB, Stein JL, van Wijnen AJ, Stein GS. Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16964-9.

  • Ghule PN, Becker KA, Harper JW, Lian JB, Stein JL, van Wijnen AJ, Stein GS. Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220(NPAT) in human embryonic stem cells. J Cell Physiol. 2007 Oct;213(1):9-17.

  • Becker KA, Stein JL, Lian JB, van Wijnen AJ, Stein GS. Establishment of histone gene regulation and cell cycle checkpoint control in human embryonic stem cells. J Cell Physiol. 2007 Feb;210(2):517-26.

  • Becker KA, Ghule PN, Therrien JA, Lian JB, Stein JL, van Wijnen AJ, Stein GS. Self-renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase. J Cell Physiol. 2006 Dec;209(3):883-93.