Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration

G. Condorelli, U. Borello, L. De Angelis, M. Latronico, D. Sirabella, M. Coletta, R. Galli, G. Balconi, A. Follenzi, G. Frati, M. G. Cusella De Angelis, L. Gioglio, S. Amuchastegui, L. Adorini, L. Naldini, A. Vescovi, E. Dejana, G. Cossu

Research output: Contribution to journalArticle

Abstract

The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.

Original languageEnglish
Pages (from-to)10733-10738
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number19
DOIs
Publication statusPublished - Sep 11 2001

Fingerprint

Cardiac Myocytes
Regeneration
Myocardium
Endothelial Cells
Neural Stem Cells
Bone Morphogenetic Protein 4
Human Umbilical Vein Endothelial Cells
von Willebrand Factor
Fibroblast Growth Factor 2
Myosins
Hematopoietic Stem Cells
Coculture Techniques
Mesenchymal Stromal Cells
Embryonic Development
Mammals
Skeletal Muscle
Stem Cells
Cell Culture Techniques
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle : Implications for myocardium regeneration. / Condorelli, G.; Borello, U.; De Angelis, L.; Latronico, M.; Sirabella, D.; Coletta, M.; Galli, R.; Balconi, G.; Follenzi, A.; Frati, G.; Cusella De Angelis, M. G.; Gioglio, L.; Amuchastegui, S.; Adorini, L.; Naldini, L.; Vescovi, A.; Dejana, E.; Cossu, G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 19, 11.09.2001, p. 10733-10738.

Research output: Contribution to journalArticle

Condorelli, G, Borello, U, De Angelis, L, Latronico, M, Sirabella, D, Coletta, M, Galli, R, Balconi, G, Follenzi, A, Frati, G, Cusella De Angelis, MG, Gioglio, L, Amuchastegui, S, Adorini, L, Naldini, L, Vescovi, A, Dejana, E & Cossu, G 2001, 'Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10733-10738. https://doi.org/10.1073/pnas.191217898
Condorelli, G. ; Borello, U. ; De Angelis, L. ; Latronico, M. ; Sirabella, D. ; Coletta, M. ; Galli, R. ; Balconi, G. ; Follenzi, A. ; Frati, G. ; Cusella De Angelis, M. G. ; Gioglio, L. ; Amuchastegui, S. ; Adorini, L. ; Naldini, L. ; Vescovi, A. ; Dejana, E. ; Cossu, G. / Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle : Implications for myocardium regeneration. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 19. pp. 10733-10738.
@article{7a9a6ec23a1c456ea3add1c105c88e15,
title = "Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration",
abstract = "The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.",
author = "G. Condorelli and U. Borello and {De Angelis}, L. and M. Latronico and D. Sirabella and M. Coletta and R. Galli and G. Balconi and A. Follenzi and G. Frati and {Cusella De Angelis}, {M. G.} and L. Gioglio and S. Amuchastegui and L. Adorini and L. Naldini and A. Vescovi and E. Dejana and G. Cossu",
year = "2001",
month = "9",
day = "11",
doi = "10.1073/pnas.191217898",
language = "English",
volume = "98",
pages = "10733--10738",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "19",

}

TY - JOUR

T1 - Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle

T2 - Implications for myocardium regeneration

AU - Condorelli, G.

AU - Borello, U.

AU - De Angelis, L.

AU - Latronico, M.

AU - Sirabella, D.

AU - Coletta, M.

AU - Galli, R.

AU - Balconi, G.

AU - Follenzi, A.

AU - Frati, G.

AU - Cusella De Angelis, M. G.

AU - Gioglio, L.

AU - Amuchastegui, S.

AU - Adorini, L.

AU - Naldini, L.

AU - Vescovi, A.

AU - Dejana, E.

AU - Cossu, G.

PY - 2001/9/11

Y1 - 2001/9/11

N2 - The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.

AB - The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.

UR - http://www.scopus.com/inward/record.url?scp=0035845530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035845530&partnerID=8YFLogxK

U2 - 10.1073/pnas.191217898

DO - 10.1073/pnas.191217898

M3 - Article

C2 - 11535818

AN - SCOPUS:0035845530

VL - 98

SP - 10733

EP - 10738

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 19

ER -