TY  - JOUR
AU  - Singh, Manvendra
AU  - Kondrashkina, Aleksandra M
AU  - Widmann, Thomas J
AU  - Cortes, Jose L
AU  - Bansal, Vikas
AU  - Wang, Jichang
AU  - Römer, Christine
AU  - Garcia-Canadas, Marta
AU  - Garcia-Perez, Jose L
AU  - Hurst, Laurence D
AU  - Izsvák, Zsuzsanna
TI  - A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass.
JO  - PLoS biology
VL  - 21
IS  - 6
SN  - 1544-9173
CY  - Lawrence, KS
PB  - PLoS
M1  - DZNE-2023-00671
SP  - e3002162
PY  - 2023
AB  - There remains much that we do not understand about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Here, we provide a multi-method analysis of the early human embryo to resolve these issues. Single-cell analysis (on multiple independent datasets), supported by embryo visualisation, uncovers a common previously uncharacterised class of cells lacking commitment markers that segregates after embryonic gene activation (EGA) and shortly after undergo apoptosis. The discovery of this cell type allows us to clearly define their viable ontogenetic sisters, these being the cells of the ICM. While ICM is characterised by the activity of an Old non-transposing endogenous retrovirus (HERVH) that acts to suppress Young transposable elements, the new cell type, by contrast, expresses transpositionally competent Young elements and DNA-damage response genes. As the Young elements are RetroElements and the cells are excluded from the developmental process, we dub these REject cells. With these and ICM being characterised by differential mobile element activities, the human embryo may be a 'selection arena' in which one group of cells selectively die, while other less damaged cells persist.
KW  - Humans
KW  - DNA Transposable Elements: genetics
KW  - Blastocyst: metabolism
KW  - Embryo, Mammalian
KW  - DNA Transposable Elements (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10281584
C6  - pmid:37339119
DO  - DOI:10.1371/journal.pbio.3002162
UR  - https://pub.dzne.de/record/258698
ER  -