| First Author | Liu H | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 1 | Pages | 108722 |
| PubMed ID | 38226173 | Mgi Jnum | J:344312 |
| Mgi Id | MGI:7575369 | Doi | 10.1016/j.isci.2023.108722 |
| Citation | Liu H, et al. (2024) Epigenetic repression of Cend1 by lysine-specific demethylase 1 is essential for murine heart development. iScience 27(1):108722 |
| abstractText | Epigenetic regulation of heart development remains incompletely understood. Here we show that LSD1, a histone demethylase, plays a crucial role in regulating cardiomyocyte proliferation during heart development. Cardiomyocyte-specific deletion of Lsd1 in mice inhibited cardiomyocyte proliferation, causing severe growth defect of embryonic and neonatal heart. In vivo RNA-seq and in vitro functional studies identified Cend1 as a target suppressed by LSD1. Lsd1 loss resulted in elevated Cend1 transcription associated with increased active histone mark H3K4me2 at Cend1 promoter. Cend1 knockdown relieved the cell-cycle arrest and proliferation defect caused by LSD1 inhibition in primary rat cardiomyocytes. Moreover, genetic deletion of Cend1 rescued cardiomyocyte proliferation defect and embryonic lethality in Lsd1 null embryos. Consistently, LSD1 promoted the cell cycle of cardiomyocytes derived from human-induced pluripotent stem cells by repressing CEND1. Together, these findings reveal an epigenetic regulatory mechanism involving the LSD1-CEND1 axis that controls cardiomyocyte proliferation essential for murine heart development. |
