Open AccessFemale human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation
Author(s) -
Tsotne Chitiashvili,
Iris Dror,
Rachel Kim,
FeiMan Hsu,
R. Sonal Chaudhari,
Erica C. Pandolfi,
Di Chen,
Simone Liebscher,
Katja SchenkeLayland,
Kathrin Plath,
Amander T. Clark
Publication year - 2020
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-020-00607-4
Subject(s) - xist , dosage compensation , x inactivation , biology , germline , x chromosome , microbiology and biotechnology , meiosis , skewed x inactivation , germ cell , genetics , gene dosage , embryo , gene , gene expression
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.