PEBC Report - Programa de Epigenética y Biología del Cáncer

SPEAKERS BIOGRAPHY AND ABSTRACT
Peter W Andrews
Peter Andrews, PhD, obtain a BSc in
Biochemistry from the University of
Leeds in 1971, and a D. Phil. in
Genetics from the University of Oxford
in 1975. Following postdoctoral
research at the Institut Pasteur in Paris
and the Sloan Kettering Institute in
New York, he was a research scientist
on the staff of the Wistar Institute of
Anatomy and Biology in Philadelphia
from 1978 to 1992. In 1992 he was appointed to the Arthur
Jackson Chair of Biomedical Research in the University of
Sheffield, where he is currently co-director of the Centre for
Stem Cell Biology. His research focuses on the biology of
pluripotent human stem cells. Among his current activities
he co-ordinates the International stem Cell Initiative, which is
focused upon characterising standard markers and culture
conditions for human ES cells. He is also the co-ordinator of
ESTOOLS, a European Integrated Project of 21 partners
under the sixth framework program.
The Centre for Stem Cell Biology
and Department of Biomedical Science,
The University of Sheffield, UK
Population Dynamics of Human ES Cell
Cultures: Self-Renewal, Adaptation and Cancer
of the population as a whole, without taking account of the
consequent heterogeneity of such cultures. Further, a
propensity for differentiation provides a basis for selective
pressures that may lead to the appearance of variant ES
cells that exhibit an increased probability of self renewal
over differentiation, or cell death through apoptosis.
Indeed human ES cell lines do tend to accumulate nonrandom
genetic changes on prolonged culture. These
genetic changes include amplifications of chromosomes
12, 17 and X similar to those seen in embryonal carcinoma
(EC) cells, the stem cells of teratocarcinomas and the
malignant counterparts of ES cells. Thus the progressive
culture adaptation of human ES cells in culture provides a
unique model that may be pertinent to the progression of
stem cell based cancers.
Accumulating evidence suggests that the ‘stem cell compartment’
in both ES and other stem cells, including cancer
stem cells, may be composed of distinct substates.
Another aspect of culture adaption of human ES cells is
that it alters the population dynamics of ES cultures, particularly
affecting the behavior of substates within the
stem cell compartment. Understanding the nature of
these substates and their interactions may provide
insights into the mechanisms that control self renewal,
commitment to differentiation and lineage selection of ES
and, ultimately iPS cells. Inevitably these same mechanisms
may also play a role in cancer progression.
A key feature of pluripotent stem cells is their ability to proliferate
indefinitely while maintaining an ability to differentiate
into all somatic cell types. Such proliferation is known as
‘self-renewal’. However, these cells may also differentiate
spontaneously, or in response to specific cues. When they
divide, stem cells must choose between self renewal and
commitment to differentiation. Further, if they commit to differentiate
they must choose between different lineages. An
understanding of the molecular mechanisms that control
these decision processes underlies any potential use of
human embryonic stem (ES) cells, or iPS cells, whether in
regenerative medicine or in other areas such as drug discovery,
toxicology or disease modeling.
Some degree of spontaneous differentiation is common in
cultures of human ES cells. This can confuse studies of
human ES cell behavior if assays are based on assessment
Selected Publications
Andrews, P.W. (2002). From teratocarcinomas to embryonic
stem cells. Phil. Trans. R. Soc. Lond. B 357, 405-417.
Baker, D.E.C., Harrison, N.J., Maltby, E., Smith, K., Moore,
H.D., Shaw, P.J., Heath, P.R., Holden, H., Andrews, P.W.,
(2007) Adaptation to culture of human embryonic stem cells
and oncogenesis in vivo. Nature Biotechnology 25: 207 –
215.
Draper J.S. Smith, K., Gokhale, P.J., Moore, H.D., Maltby, E.,
Johnson, J., Meisner, L., Zwaka, T.P., Thomson, J.A.,
Andrews, P.W. (2004) Karyotypic evolution of human
Embryonic Stem (ES) cells in culture: recurrent gain of chromosomes
17 (17q) and 12. Nat. Biotech. 22: 53-54
Enver T, Soneji S, Joshi C, Iborra F, Orntoft T, Thykjaer T, Maltby
E, Smith K, Abu Dawd R, Matin M, Gokhale P, Draper JS,
Andrews, P.W. (2005) Cellular differentiation hierarchies in
normal and culture adapted human embryonic stem cells.
Human Mol Genet. 14: 1-12.
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