PMID:17502484
| Citation |
Tateishi, K, Ashihara, E, Takehara, N, Nomura, T, Honsho, S, Nakagami, T, Morikawa, S, Takahashi, T, Ueyama, T, Matsubara, H and Oh, H (2007) Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. J. Cell. Sci. 120:1791-800 |
|---|---|
| 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 TERT(GFP)-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. |
| Links |
PubMed Online version:10.1242/jcs.006122 |
| Keywords |
Animals; Antigens, Ly/genetics; Antigens, Ly/metabolism; Apoptosis/genetics; Cell Proliferation; Cell Survival/physiology; Cells, Cultured; Clone Cells/cytology; Clone Cells/metabolism; Down-Regulation/genetics; Graft Survival/physiology; Green Fluorescent Proteins/genetics; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Transgenic; Myoblasts, Cardiac/cytology; Myoblasts, Cardiac/metabolism; Myocardial Ischemia/metabolism; Myocardial Ischemia/physiopathology; Myocardial Ischemia/therapy; Myocardium/cytology; Myocardium/metabolism; Myocytes, Cardiac/cytology; Myocytes, Cardiac/metabolism; Paracrine Communication/physiology; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; RNA Interference; Regeneration/physiology; Stem Cell Transplantation/methods; Stem Cells/cytology; Stem Cells/metabolism; Telomerase/genetics; Telomerase/metabolism |
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