Cardiac Development Long Non-Coding RNA (<i>CARDEL</i>) Is Activated during Human Heart Development and Contributes to Cardiac Specification and Homeostasis
Isabela T. Pereira,
Rubens Gomes-Júnior,
Aruana Hansel-Frose,
Rhaíza S. V. França,
Man Liu,
Hossam A. N. Soliman,
Sunny S. K. Chan,
Samuel C. Dudley,
Michael Kyba,
Bruno Dallagiovanna
Affiliations
Isabela T. Pereira
Basic Stem Cell Biology Laboratory, Instituto Carlos Chagas-FIOCRUZ-PR, Curitiba 81350-010, PR, Brazil
Rubens Gomes-Júnior
Basic Stem Cell Biology Laboratory, Instituto Carlos Chagas-FIOCRUZ-PR, Curitiba 81350-010, PR, Brazil
Aruana Hansel-Frose
Basic Stem Cell Biology Laboratory, Instituto Carlos Chagas-FIOCRUZ-PR, Curitiba 81350-010, PR, Brazil
Rhaíza S. V. França
Basic Stem Cell Biology Laboratory, Instituto Carlos Chagas-FIOCRUZ-PR, Curitiba 81350-010, PR, Brazil
Man Liu
Department of Medicine, Division of Cardiology, University of Minnesota, Minneapolis, MN 55455, USA
Hossam A. N. Soliman
Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA
Sunny S. K. Chan
Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA
Samuel C. Dudley
Department of Medicine, Division of Cardiology, University of Minnesota, Minneapolis, MN 55455, USA
Michael Kyba
Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA
Bruno Dallagiovanna
Basic Stem Cell Biology Laboratory, Instituto Carlos Chagas-FIOCRUZ-PR, Curitiba 81350-010, PR, Brazil
Successful heart development depends on the careful orchestration of a network of transcription factors and signaling pathways. In recent years, in vitro cardiac differentiation using human pluripotent stem cells (hPSCs) has been used to uncover the intricate gene-network regulation involved in the proper formation and function of the human heart. Here, we searched for uncharacterized cardiac-development genes by combining a temporal evaluation of human cardiac specification in vitro with an analysis of gene expression in fetal and adult heart tissue. We discovered that CARDEL (CARdiac DEvelopment Long non-coding RNA; LINC00890; SERTM2) expression coincides with the commitment to the cardiac lineage. CARDEL knockout hPSCs differentiated poorly into cardiac cells, and hPSC-derived cardiomyocytes showed faster beating rates after controlled overexpression of CARDEL during differentiation. Altogether, we provide physiological and molecular evidence that CARDEL expression contributes to sculpting the cardiac program during cell-fate commitment.