Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts

Sho Haginiwa, Taketaro Sadahiro, Hidenori Kojima, Mari Isomi, Fumiya Tamura, Shota Kurotsu, Hidenori Tani, Naoto Muraoka, Noriko Miyake, Koichi Miyake, Keiichi Fukuda, Masaki Ieda

Research output: Contribution to journalArticle

Abstract

Cardiovascular disease is a leading cause of death worldwide. Mammalian cardiomyocytes (CMs) proliferate during embryonic development, whereas they largely lose their regenerative capacity after birth. Defined factors expressed in cardiac progenitors or embryonic CMs may activate the cell cycle and induce CM proliferation in postnatal and adult hearts. Here, we report that the overexpression of Tbx6, enriched in the cardiac mesoderm (progenitor cells), induces CM proliferation in postnatal and adult mouse hearts. By screening 24 factors enriched in cardiac progenitors or embryonic CMs, we found that only Tbx6 could induce CM proliferation in primary cultured postnatal rat CMs. Intriguingly, it did not induce the proliferation of cardiac fibroblasts. We next generated a recombinant adeno-associated virus serotype 9 vector encoding Tbx6 (AAV9-Tbx6) for transduction into mouse CMs in vivo. The subcutaneous injection of AAV9-Tbx6 into neonatal mice induced CM proliferation in postnatal and adult mouse hearts. Mechanistically, Tbx6 overexpression upregulated multiple cell cycle activators including Aurkb, Mki67, Ccna1, and Ccnb2 and suppressed the tumor suppressor Rb1. Thus, Tbx6 promotes CM proliferation in postnatal and adult mouse hearts by modifying the expression of cell cycle regulators.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Cardiac Myocytes
Cells
Viruses
Fibroblasts
Dependovirus
Cell Cycle
Rats
Tumors
Screening
Mesoderm
Subcutaneous Injections
Embryonic Development
Cause of Death
Cardiovascular Diseases
Stem Cells
Parturition

Keywords

  • AAV9
  • Cardiomyocyte
  • Cell cycle
  • Regeneration
  • Tbx6

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts. / Haginiwa, Sho; Sadahiro, Taketaro; Kojima, Hidenori; Isomi, Mari; Tamura, Fumiya; Kurotsu, Shota; Tani, Hidenori; Muraoka, Naoto; Miyake, Noriko; Miyake, Koichi; Fukuda, Keiichi; Ieda, Masaki.

In: Biochemical and Biophysical Research Communications, 01.01.2019.

Research output: Contribution to journalArticle

Haginiwa, S, Sadahiro, T, Kojima, H, Isomi, M, Tamura, F, Kurotsu, S, Tani, H, Muraoka, N, Miyake, N, Miyake, K, Fukuda, K & Ieda, M 2019, 'Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts', Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2019.04.087
Haginiwa, Sho ; Sadahiro, Taketaro ; Kojima, Hidenori ; Isomi, Mari ; Tamura, Fumiya ; Kurotsu, Shota ; Tani, Hidenori ; Muraoka, Naoto ; Miyake, Noriko ; Miyake, Koichi ; Fukuda, Keiichi ; Ieda, Masaki. / Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts. In: Biochemical and Biophysical Research Communications. 2019.
@article{c4ef8a686230466d8b8f8b517aa2a8d1,
title = "Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts",
abstract = "Cardiovascular disease is a leading cause of death worldwide. Mammalian cardiomyocytes (CMs) proliferate during embryonic development, whereas they largely lose their regenerative capacity after birth. Defined factors expressed in cardiac progenitors or embryonic CMs may activate the cell cycle and induce CM proliferation in postnatal and adult hearts. Here, we report that the overexpression of Tbx6, enriched in the cardiac mesoderm (progenitor cells), induces CM proliferation in postnatal and adult mouse hearts. By screening 24 factors enriched in cardiac progenitors or embryonic CMs, we found that only Tbx6 could induce CM proliferation in primary cultured postnatal rat CMs. Intriguingly, it did not induce the proliferation of cardiac fibroblasts. We next generated a recombinant adeno-associated virus serotype 9 vector encoding Tbx6 (AAV9-Tbx6) for transduction into mouse CMs in vivo. The subcutaneous injection of AAV9-Tbx6 into neonatal mice induced CM proliferation in postnatal and adult mouse hearts. Mechanistically, Tbx6 overexpression upregulated multiple cell cycle activators including Aurkb, Mki67, Ccna1, and Ccnb2 and suppressed the tumor suppressor Rb1. Thus, Tbx6 promotes CM proliferation in postnatal and adult mouse hearts by modifying the expression of cell cycle regulators.",
keywords = "AAV9, Cardiomyocyte, Cell cycle, Regeneration, Tbx6",
author = "Sho Haginiwa and Taketaro Sadahiro and Hidenori Kojima and Mari Isomi and Fumiya Tamura and Shota Kurotsu and Hidenori Tani and Naoto Muraoka and Noriko Miyake and Koichi Miyake and Keiichi Fukuda and Masaki Ieda",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bbrc.2019.04.087",
language = "English",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts

AU - Haginiwa, Sho

AU - Sadahiro, Taketaro

AU - Kojima, Hidenori

AU - Isomi, Mari

AU - Tamura, Fumiya

AU - Kurotsu, Shota

AU - Tani, Hidenori

AU - Muraoka, Naoto

AU - Miyake, Noriko

AU - Miyake, Koichi

AU - Fukuda, Keiichi

AU - Ieda, Masaki

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Cardiovascular disease is a leading cause of death worldwide. Mammalian cardiomyocytes (CMs) proliferate during embryonic development, whereas they largely lose their regenerative capacity after birth. Defined factors expressed in cardiac progenitors or embryonic CMs may activate the cell cycle and induce CM proliferation in postnatal and adult hearts. Here, we report that the overexpression of Tbx6, enriched in the cardiac mesoderm (progenitor cells), induces CM proliferation in postnatal and adult mouse hearts. By screening 24 factors enriched in cardiac progenitors or embryonic CMs, we found that only Tbx6 could induce CM proliferation in primary cultured postnatal rat CMs. Intriguingly, it did not induce the proliferation of cardiac fibroblasts. We next generated a recombinant adeno-associated virus serotype 9 vector encoding Tbx6 (AAV9-Tbx6) for transduction into mouse CMs in vivo. The subcutaneous injection of AAV9-Tbx6 into neonatal mice induced CM proliferation in postnatal and adult mouse hearts. Mechanistically, Tbx6 overexpression upregulated multiple cell cycle activators including Aurkb, Mki67, Ccna1, and Ccnb2 and suppressed the tumor suppressor Rb1. Thus, Tbx6 promotes CM proliferation in postnatal and adult mouse hearts by modifying the expression of cell cycle regulators.

AB - Cardiovascular disease is a leading cause of death worldwide. Mammalian cardiomyocytes (CMs) proliferate during embryonic development, whereas they largely lose their regenerative capacity after birth. Defined factors expressed in cardiac progenitors or embryonic CMs may activate the cell cycle and induce CM proliferation in postnatal and adult hearts. Here, we report that the overexpression of Tbx6, enriched in the cardiac mesoderm (progenitor cells), induces CM proliferation in postnatal and adult mouse hearts. By screening 24 factors enriched in cardiac progenitors or embryonic CMs, we found that only Tbx6 could induce CM proliferation in primary cultured postnatal rat CMs. Intriguingly, it did not induce the proliferation of cardiac fibroblasts. We next generated a recombinant adeno-associated virus serotype 9 vector encoding Tbx6 (AAV9-Tbx6) for transduction into mouse CMs in vivo. The subcutaneous injection of AAV9-Tbx6 into neonatal mice induced CM proliferation in postnatal and adult mouse hearts. Mechanistically, Tbx6 overexpression upregulated multiple cell cycle activators including Aurkb, Mki67, Ccna1, and Ccnb2 and suppressed the tumor suppressor Rb1. Thus, Tbx6 promotes CM proliferation in postnatal and adult mouse hearts by modifying the expression of cell cycle regulators.

KW - AAV9

KW - Cardiomyocyte

KW - Cell cycle

KW - Regeneration

KW - Tbx6

UR - http://www.scopus.com/inward/record.url?scp=85064455844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064455844&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2019.04.087

DO - 10.1016/j.bbrc.2019.04.087

M3 - Article

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

ER -