Single Cell Sequencing Reveals Mechanisms of Persistent Truncus Arteriosus Formation after PDGFRα and PDGFRß Double Knockout in Cardiac Neural Crest Cells.
Genes (Basel)
; 13(10)2022 Sep 23.
Article
in En
| MEDLINE
| ID: mdl-36292593
Persistent truncus arteriosus (PTA) is an uncommon and complex congenital cardiac malformation accounting for about 1.2% of all congenital heart diseases (CHDs), which is caused by a deficiency in the embryonic heart outflow tract's (OFT) septation and remodeling. PDGFRα and PDGFRß double knockout (DKO) in cardiac neural crest cells (CNCCs) has been reported to cause PTA, but the underlying mechanisms remain unclear. Here, we constructed a PTA mouse model with PDGFRα and PDGFRß double knockout in Pax3+ CNCCs and described the condensation failure into OFT septum of CNCC-derived cells due to disturbance of cell polarity in the DKO group. In addition, we further explored the mechanism with single-cell RNA sequencing. We found that two main cell differentiation trajectories into vascular smooth muscle cells (VSMCs) from cardiomyocytes (CMs) and mesenchymal cells (MSs), respectively, were interrupted in the DKO group. The process of CM differentiation into VSMC stagnated in a transitional CM I-like state, which contributed to the failure of OFT remodeling and muscular septum formation. On the other hand, a Penk+ transitional MS II cluster closely related to cell condensation into the OFT septum disappeared, which led to the OFT's septation absence directly. In conclusion, the disturbance of CNCC-derived cells caused by PDGFRα and PDGFRß knockout can lead to the OFT septation disorder and the occurrence of PTA.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Truncus Arteriosus, Persistent
/
Neural Crest
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Genes (Basel)
Year:
2022
Document type:
Article
Affiliation country:
China
Country of publication:
Suiza