Human Molecular Genetics, ( ISI ), Year (2005-11)

Title : Cellular differentiation hierarchies in normal and culture-adapted numan embryonic stem cells ( Cellular differentiation hierarchies in normal and culture-adapted numan embryonic stem cells )

Authors: Tariq Enver , Shamit Soneji , Chirag Joshi , John Brown , Francisco Iborra , Torben Orntoft , Thomas Thykjaer , Edna Maltby , Kath Smith , Raed Abu Dawud , Mark Jones , Maryam Moghaddam Matin , Paul Gokhale , Jonathan Draper , Peter W. Andrews ,

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Human embryonic stem cell (HESC) lines vary in their characteristics and behaviour not only because they are derived from genetically outbred populations, but also because they may undergo progressive adaptation upon long-term culture in vitro. Such adaptation may reflect selection of variants with altered propensity for survival and retention of an undifferentiated phenotype. Elucidating the mechanisms involved will be important for understanding normal self-renewal and commitment to differentiation and for validating the safety of HESC-based therapy. We have investigated this process of adaptation at the cellular and molecular levels through a comparison of early passage (normal) and late passage (adapted) sublines of a single HESC line, H7. To account for spontaneous differentiation that occurs in HESC cultures, we sorted cells for SSEA3, which marks undifferentiated HESC. We show that the gene expression programmes of the adapted cells partially reflected their aberrant karyotype, but also resulted from a failure in X-inactivation, emphasizing the importance in adaptation of karyotypically silent epigenetic changes. On the basis of growth potential, ability to re-initiate ES cultures and global transcription profiles, we propose a cellular differentiation hierarchy for maintenance cultures of HESC: normal SSEA31 cells represent pluripotent stem cells. Normal SSEA32 cells have exited this compartment, but retain multilineage differentiation potential. However, adapted SSEA31 and SSEA32 cells co-segregate within the stem cell territory, implying that adaptation reflects an alteration in the balance between self-renewal and differentiation. As this balance is also an essential feature of cancer, the mechanisms of culture adaptation may mirror those of oncogenesis and tumour progression.

Keywords

human
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@article{paperid:202969,
author = {Tariq Enver and Shamit Soneji and Chirag Joshi and John Brown and Francisco Iborra and Torben Orntoft and Thomas Thykjaer and Edna Maltby and Kath Smith and Raed Abu Dawud and Mark Jones and Moghaddam Matin, Maryam and Paul Gokhale and Jonathan Draper and Peter W. Andrews},
title = {Cellular differentiation hierarchies in normal and culture-adapted numan embryonic stem cells},
journal = {Human Molecular Genetics},
year = {2005},
month = {November},
issn = {0964-6906},
keywords = {human ES},
}

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%0 Journal Article
%T Cellular differentiation hierarchies in normal and culture-adapted numan embryonic stem cells
%A Tariq Enver
%A Shamit Soneji
%A Chirag Joshi
%A John Brown
%A Francisco Iborra
%A Torben Orntoft
%A Thomas Thykjaer
%A Edna Maltby
%A Kath Smith
%A Raed Abu Dawud
%A Mark Jones
%A Moghaddam Matin, Maryam
%A Paul Gokhale
%A Jonathan Draper
%A Peter W. Andrews
%J Human Molecular Genetics
%@ 0964-6906
%D 2005

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