Aberrant genomic imprinting in rhesus monkey embryonic stem cells

Area of Science:

• Genetics
• Developmental Biology
• Stem Cell Biology

Background:

• Genomic imprinting regulates differential parental allele expression, crucial for development.
• Disrupted imprinting is linked to human diseases and tumorigenesis.
• Imprinted gene expression in primate embryonic stem cells (ESCs) remains largely uncharacterized.

Purpose of the Study:

• To investigate allele-specific expression of four imprinted genes in rhesus macaque embryos and ESCs.
• To assess the imprinting status of key genes in primate ESCs for potential therapeutic applications.

Main Methods:

• Analysis of allele-specific gene expression using PCR-based amplification and sequence analysis.
• Examination of genomic and complementary DNA from rhesus macaque embryos and ESC lines.
• Single nucleotide polymorphism (SNP) analysis to distinguish parental alleles.

Main Results:

• NDN expression was variable in blastocysts, suggesting incomplete imprinting.
• IGF2 and SNRPN showed expected paternal allele expression, while H19 showed maternal allele expression in blastocysts.
• In ESCs, NDN and SNRPN exhibited paternal allele expression, but IGF2 and H19 displayed loss of imprinting with biallelic expression.
• These aberrant imprinting patterns persisted in differentiated ESC progeny.

Conclusions:

• Rhesus macaque ESCs exhibit altered imprinting patterns compared to expected allelic expression.
• Loss of imprinting in key genes like IGF2 and H19 in ESCs has unknown implications for differentiation and in vivo function.
• Further research is needed to understand the consequences of aberrant imprinting for ESC-based regenerative medicine.