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

GNAS is a complex gene that through use of alternative first exons encodes signaling proteins Gαs and XLαs 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 Gαs, NESP55, and XLαs prior to tissue differentiation in cell cultures derived from human primordia germ cells. We found that the expression of Gαs was biallelic (maternal allele: 52.6%± 2.5%; paternal allele: 47.2%± 2.5%; p= 0.07), whereas NESP55 was expressed preferentially from the maternal allele (maternal allele: 81.9%± 10%; paternal allele: 18.1%± 10%; p= 0.002) and XLαs was preferentially expressed from the paternal allele (maternal allele: 2.7%± 0.3%; paternal allele: 97.3%± 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 XLαs occurs very early postfertilization. By contrast, mprinting of Gαs most likely occurs after 11 weeks postfertilization and after tissue differentiation.