Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration

Kento Tateishi, Eishi Ashihara, Naofumi Takehara, Tetsuya Nomura, Shoken Honsho, Takuo Nakagami, Shigehiro Morikawa, Tomosaburo Takahashi, Tomomi Ueyama, Hiroaki Matsubara, Hidemasa Oh

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Recent studies have shown that cardiac stem cells (CSCs) from the adult mammalian heart can give rise to functional cardiomyocytes; however, the definite surface markers to identify a definitive single entity of CSCs and the molecular mechanisms regulating their growth are so far unknown. Here, we demonstrate a single-cell deposition analysis to isolate individually selected CSCs from adult murine hearts and investigate the signals required for their proliferation and survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with embryonic stem (ES) cell-like and mesenchymal cell-like characteristics and are associated with telomerase reverse transcriptase (TERT). Using a transgene that expresses a GFP reporter under the control of the TERT promoter, we demonstrated that TERTGFP-positive fractions from the heart were enriched for cells expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing CSC proliferation and survival after direct cell-grafting into ischemic myocardium require Sca-1 to upregulate the secreted paracrine effectors that augment neoangiogenesis and limit cardiac apoptosis. Thus, Sca-1 might be an essential component to promote CSC proliferation and survival to directly facilitate early engraftment, and might indirectly exert the effects on late cardiovascular differentiation after CSC transplantation.

Original languageEnglish
Pages (from-to)1791-1800
Number of pages10
JournalJournal of Cell Science
Volume120
Issue number10
DOIs
Publication statusPublished - May 15 2007
Externally publishedYes

Fingerprint

Regeneration
Stem Cells
Antigens
Adult Stem Cells
Telomerase
Cell Survival
Cell Proliferation
Single-Cell Analysis
Apoptosis
Stem Cell Transplantation
Embryonic Stem Cells
Transgenes
Cardiac Myocytes
Myocardium
Up-Regulation
Growth

Keywords

  • Cardiac stem cells
  • Proliferation
  • Regeneration
  • Stem cell antigen-1
  • Survival
  • Telomerase

ASJC Scopus subject areas

  • Cell Biology

Cite this

Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. / Tateishi, Kento; Ashihara, Eishi; Takehara, Naofumi; Nomura, Tetsuya; Honsho, Shoken; Nakagami, Takuo; Morikawa, Shigehiro; Takahashi, Tomosaburo; Ueyama, Tomomi; Matsubara, Hiroaki; Oh, Hidemasa.

In: Journal of Cell Science, Vol. 120, No. 10, 15.05.2007, p. 1791-1800.

Research output: Contribution to journalArticle

Tateishi, K, Ashihara, E, Takehara, N, Nomura, T, Honsho, S, Nakagami, T, Morikawa, S, Takahashi, T, Ueyama, T, Matsubara, H & Oh, H 2007, 'Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration', Journal of Cell Science, vol. 120, no. 10, pp. 1791-1800. https://doi.org/10.1242/jcs.006122
Tateishi, Kento ; Ashihara, Eishi ; Takehara, Naofumi ; Nomura, Tetsuya ; Honsho, Shoken ; Nakagami, Takuo ; Morikawa, Shigehiro ; Takahashi, Tomosaburo ; Ueyama, Tomomi ; Matsubara, Hiroaki ; Oh, Hidemasa. / Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. In: Journal of Cell Science. 2007 ; Vol. 120, No. 10. pp. 1791-1800.
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