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Functional Cardiac Fibroblasts Derived from Human Pluripotent Stem Cells via Second Heart Field Progenitors

ABSTRACT: Functional Cardiac Fibroblasts Derived from Human Pluripotent Stem Cells via Second Heart Field Progenitors

PROVIDER: PRJNA521412 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8548580.fastq.gz	Fastqsanger.gz
	SRR8548571.fastq.gz	Fastqsanger.gz
	SRR8548572.fastq.gz	Fastqsanger.gz
	SRR8548573.fastq.gz	Fastqsanger.gz
	SRR8548574.fastq.gz	Fastqsanger.gz

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Functional Cardiac Fibroblasts Derived from Human Pluripotent Stem Cells via Second Heart Field Progenitors

Project description:Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties (EP) of the cardiomyocytes compared to co-culture with dermal fibroblasts (DFs). The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.

2019-02-08 | GSE126260 | GEO

Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors.

Project description:Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.

| S-EPMC6527555 | biostudies-literature

Subpopulations second heart field RNA-seq

Project description:Transcriptomic profiling of second heart field subpopulations FACS sorted

2020-08-31 | GSE123771 | GEO

Subpopulations second heart field ATAC-seq

Project description:Profiling of open chromatin on second heart field subpopulations FACS sorted

2020-08-18 | GSE123765 | GEO

Subpopulations second heart field ATAC-seq

Project description:Subpopulations second heart field ATAC-seq

| PRJNA509774 | ENA

Subpopulations second heart field RNA-seq

Project description:Subpopulations second heart field RNA-seq

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Dgcr8 function in the anterior second heart field

Project description:Dgcr8 function in the anterior second heart field

| PRJNA772262 | ENA

Hedgehog Molecular Networks in the Second Heart Field

Project description:Hedgehog Molecular Networks in the Second Heart Field

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A Second Heart Field-derived vasculogenic niche contributes to cardiac lymphatics

Project description:A Second Heart Field-derived vasculogenic niche contributes to cardiac lymphatics

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Cardiac progenitors instruct second heart field fate through Wnts.

Project description:The heart develops in a synchronized sequence of proliferation and differentiation of cardiac progenitor cells (CPCs) from two anatomically distinct pools of cells, the first heart field (FHF) and second heart field (SHF). Congenital heart defects arise upon dysregulation of these processes, many of which are restricted to derivatives of the FHF or SHF. Of the conserved set of signaling pathways that regulate development, the Wnt signaling pathway has long been known for its importance in SHF development. The source of such Wnts has remained elusive, though it has been postulated that these Wnts are secreted from ectodermal or endodermal sources. The central question remains unanswered: Where do these Wnts come from? Here, we show that CPCs autoregulate SHF development via Wnt through genetic manipulation of a key Wnt export protein (Wls), scRNA-seq analysis of CPCs, and use of our precardiac organoid system. Through this, we identify dysregulated developmental trajectories of anterior SHF cell fate, leading to a striking single ventricle phenotype in knockout embryos. We then applied our findings to our precardiac organoid model and found that Wnt2 is sufficient to restore SHF cell fate in our model of disrupted endogenous Wnt signaling. In this study, we provide a basis for SHF cell fate decision-proliferation vs. differentiation-autoregulated by CPCs through Wnt.

| S-EPMC9942880 | biostudies-literature

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