c-kit expression identifies cardiovascular precursors in the neonatal heart

Yvonne N. Tallini, Su Greene Kai, Michael Craven, Alyson Spealman, Martin Breitbach, James Smith, Patricia J. Fisher, Michele A Steffey, Michael Hesse, Robert M. Doran, Ashley Woods, Babu Singh, Andrew Yen, Bernd K. Fleischmann, Michael I. Kotlikoff

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Directed differentiation of embryonic stem cells indicates that mesodermal lineages in the mammalian heart (cardiac, endothelial, and smooth muscle cells) develop from a common, multipotent cardiovascular precursor. To isolate and characterize the lineage potential of a resident pool of cardiovascular progenitor cells (CPcs), we developed BAC transgenic mice in which enhanced green fluorescent protein (EGFP) is placed under control of the c-kit locus (c-kitBAC-EGFP mice). Discrete c-kit-EGFP+ cells were observed at different stages of differentiation in embryonic hearts, increasing in number to a maximum at about postnatal day (PN) 2; thereafter, EGFP + cells declined and were rarely observed in the adult heart. EGFP+ cells purified from PN 0-5 hearts were nestin+ and expanded in culture; 67% of cells were fluorescent after 9 days. Purified cells differentiated into endothelial, cardiac, and smooth muscle cells, and differentiation could be directed by specific growth factors. CPc-derived cardiac myocytes displayed rhythmic beating and action potentials characteristic of multiple cardiac cell types, similar to ES cell-derived cardiomyocytes. Single-cell dilution studies confirmed the potential of individual CPcs to form all 3 cardiovascular lineages. In adult hearts, cryoablation resulted in c-kit-EGFP+ expression, peaking 7 days postcryolesion. Expression occurred in endothelial and smooth muscle cells in the revascularizing infarct, and in terminally differentiated cardiomyocytes in the border zone surrounding the infarct. Thus, c-kit expression marks CPc in the neonatal heart that are capable of directed differentiation in vitro; however, c-kit expression in cardiomyocytes in the adult heart after injury does not identify cardiac myogenesis.

Original languageEnglish (US)
Pages (from-to)1808-1813
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number6
DOIs
StatePublished - Feb 10 2009
Externally publishedYes

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Cardiac Myocytes
Smooth Muscle Myocytes
Stem Cells
Heart Injuries
Nestin
Cryosurgery
Muscle Development
Embryonic Stem Cells
Transgenic Mice
Action Potentials
enhanced green fluorescent protein
Cell Differentiation
Intercellular Signaling Peptides and Proteins

Keywords

  • Bacterial artificial chromosome
  • Progenitor cell
  • Stem cell

ASJC Scopus subject areas

  • General

Cite this

Tallini, Y. N., Kai, S. G., Craven, M., Spealman, A., Breitbach, M., Smith, J., ... Kotlikoff, M. I. (2009). c-kit expression identifies cardiovascular precursors in the neonatal heart. Proceedings of the National Academy of Sciences of the United States of America, 106(6), 1808-1813. https://doi.org/10.1073/pnas.0808920106

c-kit expression identifies cardiovascular precursors in the neonatal heart. / Tallini, Yvonne N.; Kai, Su Greene; Craven, Michael; Spealman, Alyson; Breitbach, Martin; Smith, James; Fisher, Patricia J.; Steffey, Michele A; Hesse, Michael; Doran, Robert M.; Woods, Ashley; Singh, Babu; Yen, Andrew; Fleischmann, Bernd K.; Kotlikoff, Michael I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 6, 10.02.2009, p. 1808-1813.

Research output: Contribution to journalArticle

Tallini, YN, Kai, SG, Craven, M, Spealman, A, Breitbach, M, Smith, J, Fisher, PJ, Steffey, MA, Hesse, M, Doran, RM, Woods, A, Singh, B, Yen, A, Fleischmann, BK & Kotlikoff, MI 2009, 'c-kit expression identifies cardiovascular precursors in the neonatal heart', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 6, pp. 1808-1813. https://doi.org/10.1073/pnas.0808920106
Tallini, Yvonne N. ; Kai, Su Greene ; Craven, Michael ; Spealman, Alyson ; Breitbach, Martin ; Smith, James ; Fisher, Patricia J. ; Steffey, Michele A ; Hesse, Michael ; Doran, Robert M. ; Woods, Ashley ; Singh, Babu ; Yen, Andrew ; Fleischmann, Bernd K. ; Kotlikoff, Michael I. / c-kit expression identifies cardiovascular precursors in the neonatal heart. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 6. pp. 1808-1813.
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AU - Smith, James

AU - Fisher, Patricia J.

AU - Steffey, Michele A

AU - Hesse, Michael

AU - Doran, Robert M.

AU - Woods, Ashley

AU - Singh, Babu

AU - Yen, Andrew

AU - Fleischmann, Bernd K.

AU - Kotlikoff, Michael I.

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