A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment.

Autor: Abraham E; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Volmert B; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA., Roule T; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Huang L; Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA, USA., Yu J; Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA, USA., Williams AE; Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA, USA., Cohen HM; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Douglas A; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Megill E; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Morris A; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Stronati E; Department of Child and Adolescence Psychiatry, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Fueyo R; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA., Zubillaga M; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Elrod JW; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA., Akizu N; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Aguirre A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA., Estaras C; Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1101/2024.07.11.602981
Abstrakt: Vitamin A/Retinoic Acid (Vit A/RA) signaling is essential for heart development. In cardiac progenitor cells (CPCs), RA signaling induces the expression of atrial lineage genes while repressing ventricular genes, thereby promoting the acquisition of an atrial cardiomyocyte cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (i.e scRNAseq and snATACseq) to untreated and RA-treated human embryonic stem cells (hESCs)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP1 and TEAD4 are integrated with the atrial transcription factor enhancer network, and that YAP1 is necessary for activation of RA-enhancers in CPCs. Furthermore, in vivo analysis of control and conditionally YAP1 KO mouse embryos ( Sox2-cre ) revealed that the expression of atrial lineage genes, such as NR2F2 , is compromised by YAP1 deletion in the CPCs of the second heart field. Accordingly, we found that YAP1 is required for the formation of an atrial chamber but is dispensable for the formation of a ventricle, in hESC-derived patterned cardiac organoids. Overall, our findings revealed that YAP1 is a non-canonical effector of RA signaling essential for the acquisition of atrial lineages during cardiogenesis.
Databáze: MEDLINE