Inhibition of HDAC activity directly reprograms murine embryonic stem cells to trophoblast stem cells.
Dev Cell
; 59(16): 2101-2117.e8, 2024 Aug 19.
Article
in En
| MEDLINE
| ID: mdl-38823394
ABSTRACT
Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trophoblasts
/
Cell Differentiation
/
Histone Deacetylase Inhibitors
/
Mouse Embryonic Stem Cells
Limits:
Animals
Language:
En
Journal:
Dev Cell
/
Dev. cell
/
Developmental cell
Journal subject:
EMBRIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos