Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation.

Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation.

Nature cell biology (2020-12-02)

Tsotne Chitiashvili, Iris Dror, Rachel Kim, Fei-Man Hsu, Rohan Chaudhari, Erica Pandolfi, Di Chen, Simone Liebscher, Katja Schenke-Layland, Kathrin Plath, Amander Clark, Tsotne Chitiashvili, Iris Dror, Rachel Kim, Fei-Man Hsu, Rohan Chaudhari, Erica Pandolfi, Di Chen, Simone Liebscher, Katja Schenke-Layland, Kathrin Plath, Amander Clark

PMID33257808

ABSTRACT

X-chromosome dosage compensation in female placental mammals is achieved by X-chromosome inactivation (XCI). Human pre-implantation embryos are an exception, in which dosage compensation occurs by X-chromosome dampening (XCD). Here, we examined whether XCD extends to human prenatal germ cells given their similarities to naive pluripotent cells. We found that female human primordial germ cells (hPGCs) display reduced X-linked gene expression before entering meiosis. Moreover, in hPGCs, both X chromosomes are active and express the long non-coding RNAs X active coating transcript (XACT) and X inactive specific transcript (XIST)-the master regulator of XCI-which are silenced after entry into meiosis. We find that XACT is a hPGC marker, describe XCD associated with XIST expression in hPGCs and suggest that XCD evolved in humans to regulate X-linked genes in pre-implantation embryos and PGCs. Furthermore, we found a unique mechanism of X-chromosome regulation in human primordial oocytes. Therefore, future studies of human germline development must consider the sexually dimorphic X-chromosome dosage compensation mechanisms in the prenatal germline.

MATERIALS

Product Number

Brand

Product Description

P4832

Sigma-Aldrich

Poly-L-lysine solution, mol wt 150,000-300,000, 0.01%, sterile-filtered, BioReagent, suitable for cell culture