Imprinting Status of GaS, NESP55, and XLas in Cell Cultures Derived from Human Embryonic Germ Cells: GNAS Imprinting in Human Embryonic Germ Cells

• Published in: Clinical and translational science 2009-10, Vol.2 (5), p.355-360
• Main Authors: Crane, Janet L, Shamblott, Michael J, Axelman, Joyce, Hsu, Stephanie, Levine, Michael A, Germain-Lee, Emily L
• Format: Article
• Language: English
• ISSN: 1752-8054
• DOI: 10.1111/j.1752-8062.2009.00148.x

GNAS is a complex gene that through use of alternative first exons encodes signaling proteins G*as and XL*as plus neurosecretory protein NESP55. Tissue-specific expression of these proteins is regulated through reciprocal genomic imprinting in fully differentiated and developed tissue. Mutations in GNAS account for several human disorders, including McCune-Albright syndrome and Albright hereditary osteodystrophy, and further knowledge of GNAS imprinting may provide insights into variable phenotypes of these disorders. We therefore analyzed expression of G*as, NESP55, and XL*as prior to tissue differentiation in cell cultures derived from human primordia germ cells. We found that the expression of G*as was biallelic (maternal allele: 52.6%c 2.5%; paternal allele: 47.2%c 2.5%; p= 0.07), whereas NESP55 was expressed preferentially from the maternal allele (maternal allele: 81.9%c 10%; paternal allele: 18.1%c 10%; p= 0.002) and XL*as was preferentially expressed from the paternal allele (maternal allele: 2.7%c 0.3%; paternal allele: 97.3%c 0.3%; p= 0.007). These results demonstrate that imprinting of NESP55 occurs very early in development, although complete imprinting appears to take place later than 5--11 weeks postfertilization, and that imprinting of XL*as occurs very early postfertilization. By contrast, mprinting of G*as most likely occurs after 11 weeks postfertilization and after tissue differentiation.