Nkx2-5 represses gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis

Arianna Caprioli, Naoko Koyano-Nakagawa, Michelina Iacovino, Xiaozhong Shi, Anwarul Ferdous, Richard P. Harvey, Eric N. Olson, Michael Kyba, Daniel J. Garry

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background-: Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined. Methods and results-: Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including Gata1, in the Nkx2-5-null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5-inducible embryonic stem cell system significantly repressed Gata1 gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the Gata1 gene enhancer and represses the transcriptional activity of the Gata1 gene. Conclusions-: Our results demonstrate that the hematopoietic/ erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5.

Original languageEnglish (US)
Pages (from-to)1633-1641
Number of pages9
JournalCirculation
Volume123
Issue number15
DOIs
StatePublished - Apr 19 2011

Fingerprint

Embryonic Development
Gene Expression
Embryonic Stem Cells
Genes
Erythroid Cells
Gene Regulatory Networks
Mesoderm
Morphogenesis
Embryonic Structures
Technology
Population

Keywords

  • developmental genes
  • gene expression regulation
  • mouse
  • Nkx2-5 protein

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Nkx2-5 represses gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis. / Caprioli, Arianna; Koyano-Nakagawa, Naoko; Iacovino, Michelina; Shi, Xiaozhong; Ferdous, Anwarul; Harvey, Richard P.; Olson, Eric N.; Kyba, Michael; Garry, Daniel J.

In: Circulation, Vol. 123, No. 15, 19.04.2011, p. 1633-1641.

Research output: Contribution to journalArticle

Caprioli, Arianna ; Koyano-Nakagawa, Naoko ; Iacovino, Michelina ; Shi, Xiaozhong ; Ferdous, Anwarul ; Harvey, Richard P. ; Olson, Eric N. ; Kyba, Michael ; Garry, Daniel J. / Nkx2-5 represses gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis. In: Circulation. 2011 ; Vol. 123, No. 15. pp. 1633-1641.
@article{2dcb641724724a55817e946cf46882f1,
title = "Nkx2-5 represses gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis",
abstract = "Background-: Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined. Methods and results-: Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including Gata1, in the Nkx2-5-null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5-inducible embryonic stem cell system significantly repressed Gata1 gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the Gata1 gene enhancer and represses the transcriptional activity of the Gata1 gene. Conclusions-: Our results demonstrate that the hematopoietic/ erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5.",
keywords = "developmental genes, gene expression regulation, mouse, Nkx2-5 protein",
author = "Arianna Caprioli and Naoko Koyano-Nakagawa and Michelina Iacovino and Xiaozhong Shi and Anwarul Ferdous and Harvey, {Richard P.} and Olson, {Eric N.} and Michael Kyba and Garry, {Daniel J.}",
year = "2011",
month = "4",
day = "19",
doi = "10.1161/CIRCULATIONAHA.110.008185",
language = "English (US)",
volume = "123",
pages = "1633--1641",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "15",

}

TY - JOUR

T1 - Nkx2-5 represses gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis

AU - Caprioli, Arianna

AU - Koyano-Nakagawa, Naoko

AU - Iacovino, Michelina

AU - Shi, Xiaozhong

AU - Ferdous, Anwarul

AU - Harvey, Richard P.

AU - Olson, Eric N.

AU - Kyba, Michael

AU - Garry, Daniel J.

PY - 2011/4/19

Y1 - 2011/4/19

N2 - Background-: Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined. Methods and results-: Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including Gata1, in the Nkx2-5-null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5-inducible embryonic stem cell system significantly repressed Gata1 gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the Gata1 gene enhancer and represses the transcriptional activity of the Gata1 gene. Conclusions-: Our results demonstrate that the hematopoietic/ erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5.

AB - Background-: Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined. Methods and results-: Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including Gata1, in the Nkx2-5-null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5-inducible embryonic stem cell system significantly repressed Gata1 gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the Gata1 gene enhancer and represses the transcriptional activity of the Gata1 gene. Conclusions-: Our results demonstrate that the hematopoietic/ erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5.

KW - developmental genes

KW - gene expression regulation

KW - mouse

KW - Nkx2-5 protein

UR - http://www.scopus.com/inward/record.url?scp=79955521591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955521591&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.110.008185

DO - 10.1161/CIRCULATIONAHA.110.008185

M3 - Article

VL - 123

SP - 1633

EP - 1641

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 15

ER -