Altered patterns of differentiation in karyotypically abnormal human embryonic stem cells

Abstract

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