» Articles » PMID: 32550911

Homozygous MESP1 Knock-in Reporter HESCs Facilitated Cardiovascular Cell Differentiation and Myocardial Infarction Repair

Overview
Journal Theranostics
Date 2020 Jun 20
PMID 32550911
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

Different populations of cardiovascular progenitor cells have been shown to possess varying differentiation potentials. They have also been used to facilitate heart repair. However, sensitive reporter cell lines that mark the human cardiovascular progenitors are in short supply. MESP1 marks the earliest population of cardiovascular progenitor cells during embryo development. Here, we generated a homozygous MESP1 knock-in reporter hESC line where mTomato gene joined to the MESP1 coding region via a 2A peptide, in which both MESP1 alleles were preserved. We performed transcriptome and functional analysis of human MESP1+ cardiovascular progenitor cells and tested their therapeutic potential using a rat model of myocardial infarction. MESP1-mTomato knock-in reporter faithfully recapitulated the endogenous level of MESP1. Transcriptome analysis revealed that MESP1+ cells highly expressed early cardiovascular genes and heart development genes. The activation of MESP1 relied on the strength of canonical Wnt signaling, peak MESP1-mTomato fluorescence correlated with the window of canonical Wnt inhibition during in vitro differentiation. We further showed that MESP1 bound to the promoter of the WNT5A gene and the up-regulation of WNT5A expression suppressed canonical Wnt/β-CATENIN signaling. Moreover, induced MESP1 expression could substitute the canonical Wnt inhibition step and promote robust cardiomyocyte formation. We used a configurable, chemically defined, tri-lineage differentiation system to obtain cardiomyocytes, endothelial cells, and smooth muscle cells from MESP1+ cells at high efficiency. Finally, we showed that the engraftment of MESP1+ cells repaired rat myocardial infarction model. MESP1-mTomato reporter cells offered a useful platform to study cardiovascular differentiation from human pluripotent stem cells and explore their therapeutic potential in regenerative medicine.

Citing Articles

Gene-Edited Human-Induced Pluripotent Stem Cell Lines to Elucidate Function throughout Cardiac Differentiation.

Inacio J, Nunes M, Almeida M, Cristo F, Anjos R, Belo J Cells. 2023; 12(4).

PMID: 36831187 PMC: 9954670. DOI: 10.3390/cells12040520.


Regulatory of miRNAs in tri-lineage differentiation of C3H10T1/2.

Huang W, Wu X, Xiang S, Qiao M, Li H, Zhu Y Stem Cell Res Ther. 2022; 13(1):521.

PMID: 36414991 PMC: 9682817. DOI: 10.1186/s13287-022-03205-3.


Cardiac organoid - a promising perspective of preclinical model.

Zhao D, Lei W, Hu S Stem Cell Res Ther. 2021; 12(1):272.

PMID: 33957972 PMC: 8100358. DOI: 10.1186/s13287-021-02340-7.


Systematic analysis using a bioinformatics strategy identifies SFTA1P and LINC00519 as potential prognostic biomarkers for lung squamous cell carcinoma.

Yin Y, Yao S, Li C, Ma Y, Kang Z, Zhang J Am J Transl Res. 2021; 13(1):168-182.

PMID: 33527016 PMC: 7847518.


Cardiomyocyte Death and Genome-Edited Stem Cell Therapy for Ischemic Heart Disease.

Cho H, Cho J Stem Cell Rev Rep. 2021; 17(4):1264-1279.

PMID: 33492627 PMC: 8316208. DOI: 10.1007/s12015-020-10096-5.


References
1.
Yan L, Yang M, Guo H, Yang L, Wu J, Li R . Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nat Struct Mol Biol. 2013; 20(9):1131-9. DOI: 10.1038/nsmb.2660. View

2.
Cao N, Liang H, Huang J, Wang J, Chen Y, Chen Z . Highly efficient induction and long-term maintenance of multipotent cardiovascular progenitors from human pluripotent stem cells under defined conditions. Cell Res. 2013; 23(9):1119-32. PMC: 3773575. DOI: 10.1038/cr.2013.102. View

3.
Cohen E, Miller M, Wang Z, Moon R, Morrisey E . Wnt5a and Wnt11 are essential for second heart field progenitor development. Development. 2012; 139(11):1931-40. PMC: 3347685. DOI: 10.1242/dev.069377. View

4.
Zhu K, Wu Q, Ni C, Zhang P, Zhong Z, Wu Y . Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates. Circ Res. 2018; 122(7):958-969. DOI: 10.1161/CIRCRESAHA.117.311578. View

5.
Angers S, Moon R . Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009; 10(7):468-77. DOI: 10.1038/nrm2717. View