Cardiac progenitors instruct second heart field fate through Wnts

5Citations
Citations of this article
13Readers
Mendeley users who have this article in their library.
Get full text

Abstract

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.

References Powered by Scopus

Wntless, a Conserved Membrane Protein Dedicated to the Secretion of Wnt Proteins from Signaling Cells

597Citations
N/AReaders
Get full text

MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube

474Citations
N/AReaders
Get full text

Secretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein

467Citations
N/AReaders
Get full text

Cited by Powered by Scopus

The Trophoblast Compartment Helps Maintain Embryonic Pluripotency and Delays Differentiation towards Cardiomyocytes

5Citations
N/AReaders
Get full text

Drosophila as a Model to Understand Second Heart Field Development

2Citations
N/AReaders
Get full text

State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells

1Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Miyamoto, M., Kannan, S., Anderson, M. J., Liu, X., Suh, D., Htet, M., … Kwon, C. (2023). Cardiac progenitors instruct second heart field fate through Wnts. Proceedings of the National Academy of Sciences of the United States of America, 120(4). https://doi.org/10.1073/pnas.2217687120

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 3

60%

Lecturer / Post doc 2

40%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 4

57%

Medicine and Dentistry 1

14%

Chemical Engineering 1

14%

Neuroscience 1

14%

Article Metrics

Tooltip
Mentions
News Mentions: 1

Save time finding and organizing research with Mendeley

Sign up for free