RT Journal Article
SR Electronic
T1 Origin and segregation of the human germline
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201706
DO 10.26508/lsa.202201706
VO 6
IS 8
A1 Castillo-Venzor, Aracely
A1 Penfold, Christopher A
A1 Morgan, Michael D
A1 Tang, Walfred WC
A1 Kobayashi, Toshihiro
A1 Wong, Frederick CK
A1 Bergmann, Sophie
A1 Slatery, Erin
A1 Boroviak, Thorsten E
A1 Marioni, John C
A1 Surani, M Azim
YR 2023
UL http://www.life-science-alliance.org/content/6/8/e202201706.abstract
AB Human germline–soma segregation occurs during weeks 2–3 in gastrulating embryos. Although direct studies are hindered, here, we investigate the dynamics of human primordial germ cell (PGCs) specification using in vitro models with temporally resolved single-cell transcriptomics and in-depth characterisation using in vivo datasets from human and nonhuman primates, including a 3D marmoset reference atlas. We elucidate the molecular signature for the transient gain of competence for germ cell fate during peri-implantation epiblast development. Furthermore, we show that both the PGCs and amnion arise from transcriptionally similar TFAP2A-positive progenitors at the posterior end of the embryo. Notably, genetic loss of function experiments shows that TFAP2A is crucial for initiating the PGC fate without detectably affecting the amnion and is subsequently replaced by TFAP2C as an essential component of the genetic network for PGC fate. Accordingly, amniotic cells continue to emerge from the progenitors in the posterior epiblast, but importantly, this is also a source of nascent PGCs.