The nature of embryonic stem cell pluripotency
Pluripotency is the potential of a cell to develop into nearly every mature cell type in the body. This
remarkable biological status is restricted to cells in the early embryo and to germ cells. The underlying concept of
pluripotency provides not only a unique basis for our understanding of the molecular processes involved in the cellular
specification of the early embryo in vivo, but also for our understanding of the basic biology of pluripotent
cell lines derived from mammalian pre-implantation embryos in vitro. In particular, embryonic stem (ES) cell
lines have attracted interest because of their potential usefulness for cellular therapies. ES cells have been derived
from pre-implantation embryos of different mammalian species. These cells demonstrate remarkable properties in cell
culture: they can be expanded without limit and are pluripotent. Although several genes essential for maintaining
pluripotency have been identified in ES cells, little is known about why some cells are pluripotent while others are
restricted in their developmental potential.
The long-term goal of our laboratory is to develop a greater understanding of ES cell pluripotency in mouse
and human ES cells, which offer unlimited materials for investigating the molecular mechanisms of pluripotency. This
knowledge is of great value, as it may allow us to develop strategies for reprogramming other cell types into
pluripotent cells. This would allow the use of reprogrammed cells in medical settings, thus bypassing many of the
ethical concerns surrounding the use of ES cells. In addition, an in-depth examination of ES cell pluripotency may
improve our understanding of adult stem cell types and cancer stem cells, which share some features with ES cells.
Our current investigations are focused on determining how undifferentiated cells decide when to undergo
programmed cell death and when to differentiate. We are developing strategies to identify novel molecular targets of the
programmed cell death pathway and differentiation machinery in ES cells, and will then examine the mechanisms by which
these molecules control the chromatin changes associated with pluripotency. Our future work will include investigations
into the true origin of ES cells, which is currently unknown. Identification of the cell type in the pre-implantation
embryo that most closely resembles ES cells will provide new insights into pluripotency.
In this way, our laboratory hopes to make important new advances towards a greater understanding of
pluripotency and its use in medical and nonmedical settings.
Selected Publications
Xu RH, Chen X, Li DS, Li R, Addicks GC, Glennon C, Zwaka TP, Thomson JA (2003) BMP4 initiates human
embryonic stem cell differentiation to trophoblast. Nature Biotechnology 20:1261-1264.
Zwaka TP, Thomson JA (2003) Homologous recombination in human embryonic stem cells. Nature
Biotechnology 21:319-321.
Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2004)
Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nature Biotechnology 22:53-54.
Zwaka TP, Thomson JA (2004) Homologous recombination in human embryonic stem cells. In Handbook of Stem Cells,
vol 2: Embryonic Stem Cells, (ed. R. P. Lanza). Elsevier Science: San Diego.
Zwaka TP, Thomson JA (2005) A germ cell origin of embryonic stem cells? Development 132:227-233.
Zwaka TP, Thomson JA (2005) Differentiation of human embryonic stem cells occurs through symmetric cell
division. Stem Cells 23:146-149.
Contact Information
- Thomas P. Zwaka, M.D., Ph.D.
- Center for Cell and Gene Therapy
- Baylor College of Medicine
- One Baylor Plaza N1030
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-1272
- Fax: (713) 798-
- E-mail: tpzwaka@bcm.tmc.edu
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