Tbx1 regulates proliferation and differentiation of multipotent heart progenitors

Li Chen, Filomena Gabriella Fulcoli, Susan Tang, Antonio Baldini

Research output: Contribution to journalArticle

Abstract

Rationale: TBX1 encodes a T-box transcription factor implicated in DiGeorge syndrome, which affects the development of many organs, including the heart. Loss of Tbx1 results into hypoplasia of heart regions derived from the second heart field, a population of cardiac progenitors cells (CPCs). Thus, we hypothesized that Tbx1 is an important player in the biology of CPCs. Objective: We asked whether Tbx1 is expressed in multipotent CPCs and, if so, what role it may play in them. Methods and Results: We used clonal analysis of Tbx1 -expressing cells and loss and gain of function models, in vivo and in vitro, to define the role of Tbx1 in CPCs. We found that Tbx1 is expressed in multipotent heart progenitors that, in clonal assays, can give rise to 3 heart lineages expressing endothelial, smooth muscle and cardiomyocyte markers. In multipotent cells, Tbx1 stimulates proliferation, explaining why Tbx1-/- embryos have reduced proliferation in the second heart field. In this population, Tbx1 is expressed while cells are undifferentiated and it disappears with the onset of muscle markers. Loss of Tbx1 results in premature differentiation, whereas gain results in reduced differentiation in vivo. We found that Tbx1 binds serum response factor, a master regulator of muscle differentiation, and negatively regulates its level. Conclusions: The Tbx1 protein marks CPCs, supports their proliferation, and inhibits their differentiation. We propose that Tbx1 is a key regulator of CPC homeostasis as it modulates positively their proliferation and negatively their differentiation.

Original languageEnglish
Pages (from-to)842-851
Number of pages10
JournalCirculation Research
Volume105
Issue number9
DOIs
Publication statusPublished - Oct 23 2009

Fingerprint

Stem Cells
Serum Response Factor
DiGeorge Syndrome
Muscles
Cardiac Myocytes
Population
Smooth Muscle
Homeostasis
Transcription Factors
Embryonic Structures
Proteins

Keywords

  • Cardiac differentiation
  • Cardiac progenitor cells
  • Serum response factor
  • T-box transcription factors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tbx1 regulates proliferation and differentiation of multipotent heart progenitors. / Chen, Li; Fulcoli, Filomena Gabriella; Tang, Susan; Baldini, Antonio.

In: Circulation Research, Vol. 105, No. 9, 23.10.2009, p. 842-851.

Research output: Contribution to journalArticle

Chen, Li ; Fulcoli, Filomena Gabriella ; Tang, Susan ; Baldini, Antonio. / Tbx1 regulates proliferation and differentiation of multipotent heart progenitors. In: Circulation Research. 2009 ; Vol. 105, No. 9. pp. 842-851.
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