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Tcf7l1 directly regulates cardiomyocyte differentiation in embryonic stem cells.

ABSTRACT: The T-cell factor/lymphoid enhancer factor (TCF/LEF) family protein Tcf7l1 is highly abundant in embryonic stem cells (ESCs), regulating pluripotency and preparing epiblasts for further differentiation. Defects in the cardiovascular system in Tcf7l1-null mouse were considered secondary to mesoderm malformation. Here, we used temporally controlled Tcf7l1 expression in Tcf7l1-null ESCs to address whether Tcf7l1 directly contributes to cardiac forward programming. Tcf7l1 knockout during differentiation impaired cardiomyocyte formation but did not affect mesoderm formation. Tcf7l1-null ESCs showed delay in mesoderm formation, but once completed, ectopic Tcf7l1 augmented cardiomyocyte differentiation. Further, Tcf7l1-VP16 and Tcf7l1dN showed procardiac activity whereas Tcf7l1-En was ineffective. Our results support that Tcf7l1 contributes to cardiac lineage development as a ?-catenin-independent transactivator of cardiac genes.

SUBMITTER: Liang R

PROVIDER: S-EPMC6190650 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Tcf7l1 directly regulates cardiomyocyte differentiation in embryonic stem cells.

Liang Rui R Liu Yu Y

Stem cell research & therapy 20181011 1

The T-cell factor/lymphoid enhancer factor (TCF/LEF) family protein Tcf7l1 is highly abundant in embryonic stem cells (ESCs), regulating pluripotency and preparing epiblasts for further differentiation. Defects in the cardiovascular system in Tcf7l1-null mouse were considered secondary to mesoderm malformation. Here, we used temporally controlled Tcf7l1 expression in Tcf7l1-null ESCs to address whether Tcf7l1 directly contributes to cardiac forward programming. Tcf7l1 knockout during differentia ...[more]

PMID: 30326964

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