Altered patterns of differentiation in karyotypically abnormal human embryonic stem cells

Area of Science:

• Stem Cell Biology
• Developmental Biology
• Genetics

Background:

• Human embryonic stem (hES) cells adapt during prolonged culture, often acquiring karyotypic abnormalities.
• This adaptation is characterized by faster proliferation and increased cloning efficiency.

Purpose of the Study:

• To investigate if culture adaptation influences the differentiation patterns of hES cells.
• To compare gene expression in embryoid bodies derived from karyotypically normal and abnormal hES cell lines.

Main Methods:

• Comparison of gene expression in embryoid bodies from early passage (normal) and late passage (abnormal) hES cell lines.
• Analysis of genes indicative of distinct embryonic lineages.

Main Results:

• Embryoid bodies from both normal and adapted hES cells showed extensive differentiation.
• Culture-adapted hES cells exhibited altered gene expression patterns compared to normal cells.
• A marked loss of alphafetoprotein induction in adapted cells indicated reduced capacity for extra-embryonic endoderm differentiation.

Conclusions:

• Culture adaptation in hES cells leads to altered differentiation patterns, notably a reduced capacity for extra-embryonic endoderm formation.
• These changes may confer a growth advantage to genetically variant cells by promoting self-renewal over differentiation.