Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use o...

Full description

Saved in:
Bibliographic Details
Main Authors: Ioannis Kokkinopoulos, Hidekazu Ishida, Rie Saba, Prashant Ruchaya, Claudia Cabrera, Monika Struebig, Michael Barnes, Anna Terry, Masahiro Kaneko, Yasunori Shintani, Steven Coppen, Hidetaka Shiratori, Torath Ameen, Charles Mein, Hiroshi Hamada, Ken Suzuki, Kenta Yashiro
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0140831
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850162301620977664
author Ioannis Kokkinopoulos
Hidekazu Ishida
Rie Saba
Prashant Ruchaya
Claudia Cabrera
Monika Struebig
Michael Barnes
Anna Terry
Masahiro Kaneko
Yasunori Shintani
Steven Coppen
Hidetaka Shiratori
Torath Ameen
Charles Mein
Hiroshi Hamada
Ken Suzuki
Kenta Yashiro
author_facet Ioannis Kokkinopoulos
Hidekazu Ishida
Rie Saba
Prashant Ruchaya
Claudia Cabrera
Monika Struebig
Michael Barnes
Anna Terry
Masahiro Kaneko
Yasunori Shintani
Steven Coppen
Hidetaka Shiratori
Torath Ameen
Charles Mein
Hiroshi Hamada
Ken Suzuki
Kenta Yashiro
author_sort Ioannis Kokkinopoulos
collection DOAJ
description In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.
format Article
id doaj-art-68625e7bac9c4986b217e49e1b2d98f6
institution OA Journals
issn 1932-6203
language English
publishDate 2015-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-68625e7bac9c4986b217e49e1b2d98f62025-08-20T02:22:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e014083110.1371/journal.pone.0140831Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.Ioannis KokkinopoulosHidekazu IshidaRie SabaPrashant RuchayaClaudia CabreraMonika StruebigMichael BarnesAnna TerryMasahiro KanekoYasunori ShintaniSteven CoppenHidetaka ShiratoriTorath AmeenCharles MeinHiroshi HamadaKen SuzukiKenta YashiroIn the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.https://doi.org/10.1371/journal.pone.0140831
spellingShingle Ioannis Kokkinopoulos
Hidekazu Ishida
Rie Saba
Prashant Ruchaya
Claudia Cabrera
Monika Struebig
Michael Barnes
Anna Terry
Masahiro Kaneko
Yasunori Shintani
Steven Coppen
Hidetaka Shiratori
Torath Ameen
Charles Mein
Hiroshi Hamada
Ken Suzuki
Kenta Yashiro
Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
PLoS ONE
title Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
title_full Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
title_fullStr Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
title_full_unstemmed Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
title_short Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
title_sort single cell expression profiling reveals a dynamic state of cardiac precursor cells in the early mouse embryo
url https://doi.org/10.1371/journal.pone.0140831
work_keys_str_mv AT ioanniskokkinopoulos singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT hidekazuishida singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT riesaba singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT prashantruchaya singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT claudiacabrera singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT monikastruebig singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT michaelbarnes singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT annaterry singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT masahirokaneko singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT yasunorishintani singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT stevencoppen singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT hidetakashiratori singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT torathameen singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT charlesmein singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT hiroshihamada singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT kensuzuki singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo
AT kentayashiro singlecellexpressionprofilingrevealsadynamicstateofcardiacprecursorcellsintheearlymouseembryo