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Cardiac Transcription Factors Driven Lineage-Specification of Adult Stem Cells

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Abstract

Differentiation of human bone marrow mesenchymal stem cells (hBMSC) into the cardiac lineage has been assayed using different approaches such as coculture with cardiac or embryonic cells, treatment with factors, or by seeding cells in organotypic cultures. In most cases, differentiation was evaluated in terms of expression of cardiac-specific markers at protein or molecular level, electrophysiological properties, and formation of sarcomers in differentiated cells. As observed in embryonic stem cells and cardiac progenitors, differentiation of MSC towards the cardiac lineage was preceded by translocation of NKX2.5 and GATA4 transcription factors to the nucleus. Here, we induce differentiation of hBMSC towards the cardiac lineage using coculture with neonatal rat cardiomyocytes. Although important ultrastructural changes occurred during the course of differentiation, sarcomerogenesis was not fully achieved even after long periods of time. Nevertheless, we show that the main cardiac markers, NKX2.5 and GATA4, translocate to the nucleus in a process characteristic of cardiac specification.

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Acknowledgments

Supported by grants from the Instituto de Salud Carlos III for the Regenerative Medicine Program of Valencian Community, the RETICS program and from the FIS (PI07/784, CP08/80). PS is a research Bellow (Miguel Servet Program) at Fundación para la Investigación Hospital la Fe. AA and CG are postdoctoral fellows from the Centro de Investigación Principe Felipe.

We are indebted to Dr. A Chapel for the gift of pSF-G13 cell line. We thank A. Hernández and E. Lafuente from the Service of Confocal microscopy at CIPF for technical assistance, and M. Soriano for acquisition of electron microscopy micrographs.

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Authors and Affiliations

  1. Centro de Investigación Príncipe Felipe, Valencia, Spain

    Ana Armiñán, Carolina Gandía, José Manuel García-Verdugo, Elisa Lledó, José Luis Mullor, José Anastasio Montero & Pilar Sepúlveda

  2. Instituto Cavanilles, Universidad de Valencia, Valencia, Spain

    José Manuel García-Verdugo

  3. Fundación para la Investigación Hospital Universitario La Fe, Valencia, Spain

    José Anastasio Montero & Pilar Sepúlveda

  4. Regenerative Medicine and Heart Transplantation Unit, Fundación para la Investigación Hospital Universitario la Fe, Avda. Campanar 21, 46009, Valencia, Spain

    Pilar Sepúlveda

Authors
  1. Ana Armiñán
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  2. Carolina Gandía
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  3. José Manuel García-Verdugo
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  4. Elisa Lledó
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  5. José Luis Mullor
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  7. Pilar Sepúlveda
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Correspondence to Pilar Sepúlveda.

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Armiñán, A., Gandía, C., García-Verdugo, J.M. et al. Cardiac Transcription Factors Driven Lineage-Specification of Adult Stem Cells. J. of Cardiovasc. Trans. Res. 3, 61–65 (2010). https://doi.org/10.1007/s12265-009-9144-3

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  • DOI: https://doi.org/10.1007/s12265-009-9144-3

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