Foxc1 Regulates Early Cardiomyogenesis and Functional Properties of Embryonic Stem Cell Derived Cardiomyocytes

Stem Cells
Erin LambersTsutomu Kume

Abstract

Embryonic Stem Cells (ESCs) hold great potential for regeneration of damaged myocardium, however the molecular circuitry that guides ESC differentiation into cardiomyocytes remains poorly understood. This is exemplified by the elusive role of the transcription factor, Foxc1, during cardiac development. The only known Foxc1 target during heart development is Tbx1. Because Foxc1 null mice contain heart mutations that are far more severe than Tbx1 null mice, it is likely that Foxc1 has additional regulatory roles during heart development. The goal of our study was to test whether Foxc1 is critical for ESC differentiation into functional cardiomyocytes through proper regulation of specific downstream gene networks. Converging evidence from Foxc1 deficient and overexpression ESC models reveals a close relationship between Foxc1 levels and early cardiomyogenic factors Isl1, Mef2c, and Nkx2.5 and also the production of functional cardiomyocytes. We show Foxc1 regulates early cardiomyogenesis during a specific window of differentiation, D4-D6. Through whole transcriptome RNA-sequencing analysis, we report pathways regulated by Foxc1 involved in cardiac function including actin cytoskeleton, cell adhesion, tight and gap junctions, and c...Continue Reading

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Citations

Mar 20, 2018·Oncotarget·Jinhua WangGuanhua Du
Sep 21, 2018·Experimental and Therapeutic Medicine·Zhongjun LiuXiongqun Zeng
Sep 24, 2020·Oxidative Medicine and Cellular Longevity·Lan ZhaoShaoheng Zhang
Jul 29, 2020·Human Molecular Genetics·Jesús-José Ferre-FernándezElena V Semina
Jul 8, 2017·Molecular Cancer Research : MCR·Alex HopkinsFred B Berry

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