Spatiotemporal analysis of cardiac progenitor cells reveals migratory characteristics during epithelial-mesenchymal transition
Abstract Body: Introduction Congenital heart defects (CHD) are one of the most common types of birth defects, with a rising prevalence in mild types. The most frequent CHDs include anomalies in the cardiac outflow tract (OFT), which mainly derives from multipotent cardiac progenitor cells termed second heart field (SHF). Hence, dysregulation of highly synchronized, chronological sequence of proliferation and differentiation of SHF cells could lead to severe CHDs. As the SHF contributes entirely to the OFT, mutations in the SHF-related genes lead to major arterial pole defects which account for one third of CHDs in newborn children. Investigating how these genes regulate cell-cell behavior and communication is of vital importance. Hypothesis and Methods In this study, we employed a multidimensional approach to assess the hypothesis that the dynamic behavior of SHFs is regulated by key genes implicated in CHD pathogenesis. Leveraging single-cell RNA sequencing (RNA-seq) data obtained from experimentally dissected mouse OFT, we delineated distinct epithelial-to-mesenchymal transition states within SHF cell populations. Additionally, we developed a quantitative metric to assess SHF cell’s migratory level and integrated it with spatial transcriptomic analyses to map the developmental trajectory of SHFs. Results and Conclusion Through spatiotemporal analysis, we identified a panel of key genes associated with SHF migration, shedding light on the molecular mechanisms underlying OFT development during early embryonic stages. Furthermore, we leveraged the data from The Pediatric Cardiac Genomics Consortium (PCGC) study (phs001194.v3.p2) which comprises a large cohort of CHD patients (13716 participants) and a proportion of 21.68% identified with OFT obstruction in its sub-study. In conclusion, using these datasets and quantitative metric being developed, we validated the SHF-derived genes in the PCGC participants and revealed specific expression patterns of these genes associated with OFT-specific CHDs. These results would benefit the understanding of the genetic regulation of SHF proliferation and differentiation, which is crucial for early detection and precise surgical intervention in CHD patients.
Li, Jing
( TAMU Health Science Center
, Houston
, Texas
, United States
)
Zhang, Ke
( TAMU Health Science Center
, Houston
, Texas
, United States
)
Author Disclosures:
Jing Li:DO NOT have relevant financial relationships
| Ke Zhang:No Answer