Int. J. Dev. Biol. 55: 175 - 180 (2011)

https://doi.org/10.1387/ijdb.103177af

Vol 55, Issue 2

Altered patterns of differentiation in karyotypically abnormal human embryonic stem cells

Original Article | Published: 8 June 2011

Alireza Fazeli^*,1, Chee-Gee Liew^2,3, Maryam M. Matin⁴, Sarah Elliott¹, Laurent F.C. Jeanmeure⁵, Phillip C. Wright⁶, Harry Moore^1,2 and Peter W. Andrews²

¹The University of Sheffield, Academic Unit of Reproductive and Developmental Medicine, Sheffield, UK, ²Centre for Stem Cell Biology and Department of Biomedical Science, University of Sheffield, Sheffield, UK, ³UCR Stem Cell Center, University of California, CA, USA, ⁴Department of Biology and Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran, ⁵Polymer Composites Research Group, Department of Mechanical, Materials and Manufacturing Engineering, University of Nottingham, Nottingham, UK and ⁶Biological and Environmental Systems Group, Department of Chemical and Process Engineering, The University of Sheffield, Sheffield, UK

Abstract

Upon prolonged culture, human embryonic stem (hES) cells undergo adaptation, exhibiting decreased population doubling times and increased cloning efficiencies, often associated with karyotypic changes. To test whether culture adaptation influences the patterns of differentiation of hES cells, we compared the expression of genes indicative of distinct embryonic lineages in the embryoid bodies produced from two early passage, karyotypically normal hES cell lines, and two late passage, karyotypically abnormal hES cell lines. One of the abnormal lines was a subline of one of the normal early passage lines. The embryoid bodies from each of the lines showed evidence of extensive differentiation. However, there were differences in the expression of several genes, indicating that the culture adapted hES cells show altered patterns of differentiation compared to karyotypically normal hES cells. The loss of induction of alphafetoprotein in the culture-adapted cells was especially marked, suggesting that they had a reduced capacity to produce extra-embryonic endoderm. These changes may contribute to the growth advantages of genetically variant cells, not only by reflecting an increased tendency to self renewal rather than to differentiate, but also by reducing spontaneous differentiation to derivatives that themselves may produce factors that could induce further differentiation of undifferentiated stem cells.

Keywords

human embryonic stem cell, differentiation