Sca-1 expression is associated with decreased cardiomyogenic differentiation potential of skeletal muscle-derived adult primitive cells

Ewa K. Zuba-Surma, Ahmed Abdel-Latif, Jamie Case, Sumit Tiwari, Greg Hunt, Magda Kucia, Robert J. Vincent, Smita Ranjan, Mariusz Z. Ratajczak, Edward Srour, Roberto Bolli, Buddhadeb Dawn

Research output: Contribution to journalArticle

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Abstract

Adult stem cells from skeletal muscle (SM) have been shown to differentiate into multiple lineages. The impact of stem cell antigen-1 (Sca-1) expression on cardiomyogenic differentiation potential of SM-derived primitive cells remains unknown. Cardiomyogenic differentiation was induced in freshly isolated or culture-expanded Sca-1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells isolated from SM of C57BL/6 mice. Expression of mRNA of cardiac-specific antigens and those associated with pluripotency was examined by real-time RT-PCR. Phenotypic analysis of expanded cells was performed during each passage by flow cytometry. Cardiomyocytic differentiation in vitro was verified by morphologic analysis, immunocytochemistry, and contractile properties. In freshly isolated cells, compared with unfractionated SM-derived cells as well as SM+ cells, mRNA expression of cardiac-specific antigens and those associated with cellular pluripotency was greater in SM- cells. Compared with SM- cells, SM+ cells exhibited greater expansion capacity. Freshly isolated SM- cells exhibited greater cardiac differentiation potential compared with freshly isolated SM+ cells (21.8 ± 0.3% of SM- cells positive for cardiac markers vs. 9.1 ± 0.7% of SM+ cells, P = 0.00009). Differentiated SM- cells acquired a cardiomyocytic phenotype and exhibited spontaneous rhythmic contractions in vitro. The number of Sca-1+ cells in the SM- population increased markedly with time (0.9 ± 0.1% in freshly isolated cells vs. 11.9 ± 0.9% after the first passage vs. 99.0 ± 0.6% after the second passage). This increase in Sca-1 expression was associated with a marked decline in the expression of cardiac markers following differentiation induction in culture-expanded SM- cells (21.8 ± 0.3% in unexpanded cells vs. 16.6 ± 1.3% after the first passage vs. 6.0 ± 0.5% after the second passage, P = 0.00001 vs. unexpanded cells). In contrast, the SM+ cells did not exhibit any consistent pattern in either phenotypic or differentiation capability with expansion. We conclude that SM- cells are inherently predisposed to undergo cardiac differentiation and are enriched in markers of pluripotency. While both Sca-1+ and Sca-1- primitive cells from SM can undergo cardiac differentiation, Sca-1- cells exhibit greater cardiomyogenic potential, and the appearance of Sca-1 during expansion is associated with a decline in cardiac differentiation plasticity.

Original languageEnglish
Pages (from-to)650-660
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume41
Issue number4
DOIs
StatePublished - Oct 2006

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Skeletal Muscle
Stem Cells
Antigens
Muscle Cells
CD45 Antigens
Messenger RNA
Adult Stem Cells
Differentiation Antigens
Inbred C57BL Mouse
Real-Time Polymerase Chain Reaction
Flow Cytometry

Keywords

  • Cardiac regeneration
  • Cardiomyocyte differentiation
  • Pluripotency
  • Sca-1
  • Skeletal muscle
  • Stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Sca-1 expression is associated with decreased cardiomyogenic differentiation potential of skeletal muscle-derived adult primitive cells. / Zuba-Surma, Ewa K.; Abdel-Latif, Ahmed; Case, Jamie; Tiwari, Sumit; Hunt, Greg; Kucia, Magda; Vincent, Robert J.; Ranjan, Smita; Ratajczak, Mariusz Z.; Srour, Edward; Bolli, Roberto; Dawn, Buddhadeb.

In: Journal of Molecular and Cellular Cardiology, Vol. 41, No. 4, 10.2006, p. 650-660.

Research output: Contribution to journalArticle

Zuba-Surma, EK, Abdel-Latif, A, Case, J, Tiwari, S, Hunt, G, Kucia, M, Vincent, RJ, Ranjan, S, Ratajczak, MZ, Srour, E, Bolli, R & Dawn, B 2006, 'Sca-1 expression is associated with decreased cardiomyogenic differentiation potential of skeletal muscle-derived adult primitive cells', Journal of Molecular and Cellular Cardiology, vol. 41, no. 4, pp. 650-660. https://doi.org/10.1016/j.yjmcc.2006.07.011
Zuba-Surma, Ewa K. ; Abdel-Latif, Ahmed ; Case, Jamie ; Tiwari, Sumit ; Hunt, Greg ; Kucia, Magda ; Vincent, Robert J. ; Ranjan, Smita ; Ratajczak, Mariusz Z. ; Srour, Edward ; Bolli, Roberto ; Dawn, Buddhadeb. / Sca-1 expression is associated with decreased cardiomyogenic differentiation potential of skeletal muscle-derived adult primitive cells. In: Journal of Molecular and Cellular Cardiology. 2006 ; Vol. 41, No. 4. pp. 650-660.
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abstract = "Adult stem cells from skeletal muscle (SM) have been shown to differentiate into multiple lineages. The impact of stem cell antigen-1 (Sca-1) expression on cardiomyogenic differentiation potential of SM-derived primitive cells remains unknown. Cardiomyogenic differentiation was induced in freshly isolated or culture-expanded Sca-1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells isolated from SM of C57BL/6 mice. Expression of mRNA of cardiac-specific antigens and those associated with pluripotency was examined by real-time RT-PCR. Phenotypic analysis of expanded cells was performed during each passage by flow cytometry. Cardiomyocytic differentiation in vitro was verified by morphologic analysis, immunocytochemistry, and contractile properties. In freshly isolated cells, compared with unfractionated SM-derived cells as well as SM+ cells, mRNA expression of cardiac-specific antigens and those associated with cellular pluripotency was greater in SM- cells. Compared with SM- cells, SM+ cells exhibited greater expansion capacity. Freshly isolated SM- cells exhibited greater cardiac differentiation potential compared with freshly isolated SM+ cells (21.8 ± 0.3{\%} of SM- cells positive for cardiac markers vs. 9.1 ± 0.7{\%} of SM+ cells, P = 0.00009). Differentiated SM- cells acquired a cardiomyocytic phenotype and exhibited spontaneous rhythmic contractions in vitro. The number of Sca-1+ cells in the SM- population increased markedly with time (0.9 ± 0.1{\%} in freshly isolated cells vs. 11.9 ± 0.9{\%} after the first passage vs. 99.0 ± 0.6{\%} after the second passage). This increase in Sca-1 expression was associated with a marked decline in the expression of cardiac markers following differentiation induction in culture-expanded SM- cells (21.8 ± 0.3{\%} in unexpanded cells vs. 16.6 ± 1.3{\%} after the first passage vs. 6.0 ± 0.5{\%} after the second passage, P = 0.00001 vs. unexpanded cells). In contrast, the SM+ cells did not exhibit any consistent pattern in either phenotypic or differentiation capability with expansion. We conclude that SM- cells are inherently predisposed to undergo cardiac differentiation and are enriched in markers of pluripotency. While both Sca-1+ and Sca-1- primitive cells from SM can undergo cardiac differentiation, Sca-1- cells exhibit greater cardiomyogenic potential, and the appearance of Sca-1 during expansion is associated with a decline in cardiac differentiation plasticity.",
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AU - Zuba-Surma, Ewa K.

AU - Abdel-Latif, Ahmed

AU - Case, Jamie

AU - Tiwari, Sumit

AU - Hunt, Greg

AU - Kucia, Magda

AU - Vincent, Robert J.

AU - Ranjan, Smita

AU - Ratajczak, Mariusz Z.

AU - Srour, Edward

AU - Bolli, Roberto

AU - Dawn, Buddhadeb

PY - 2006/10

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N2 - Adult stem cells from skeletal muscle (SM) have been shown to differentiate into multiple lineages. The impact of stem cell antigen-1 (Sca-1) expression on cardiomyogenic differentiation potential of SM-derived primitive cells remains unknown. Cardiomyogenic differentiation was induced in freshly isolated or culture-expanded Sca-1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells isolated from SM of C57BL/6 mice. Expression of mRNA of cardiac-specific antigens and those associated with pluripotency was examined by real-time RT-PCR. Phenotypic analysis of expanded cells was performed during each passage by flow cytometry. Cardiomyocytic differentiation in vitro was verified by morphologic analysis, immunocytochemistry, and contractile properties. In freshly isolated cells, compared with unfractionated SM-derived cells as well as SM+ cells, mRNA expression of cardiac-specific antigens and those associated with cellular pluripotency was greater in SM- cells. Compared with SM- cells, SM+ cells exhibited greater expansion capacity. Freshly isolated SM- cells exhibited greater cardiac differentiation potential compared with freshly isolated SM+ cells (21.8 ± 0.3% of SM- cells positive for cardiac markers vs. 9.1 ± 0.7% of SM+ cells, P = 0.00009). Differentiated SM- cells acquired a cardiomyocytic phenotype and exhibited spontaneous rhythmic contractions in vitro. The number of Sca-1+ cells in the SM- population increased markedly with time (0.9 ± 0.1% in freshly isolated cells vs. 11.9 ± 0.9% after the first passage vs. 99.0 ± 0.6% after the second passage). This increase in Sca-1 expression was associated with a marked decline in the expression of cardiac markers following differentiation induction in culture-expanded SM- cells (21.8 ± 0.3% in unexpanded cells vs. 16.6 ± 1.3% after the first passage vs. 6.0 ± 0.5% after the second passage, P = 0.00001 vs. unexpanded cells). In contrast, the SM+ cells did not exhibit any consistent pattern in either phenotypic or differentiation capability with expansion. We conclude that SM- cells are inherently predisposed to undergo cardiac differentiation and are enriched in markers of pluripotency. While both Sca-1+ and Sca-1- primitive cells from SM can undergo cardiac differentiation, Sca-1- cells exhibit greater cardiomyogenic potential, and the appearance of Sca-1 during expansion is associated with a decline in cardiac differentiation plasticity.

AB - Adult stem cells from skeletal muscle (SM) have been shown to differentiate into multiple lineages. The impact of stem cell antigen-1 (Sca-1) expression on cardiomyogenic differentiation potential of SM-derived primitive cells remains unknown. Cardiomyogenic differentiation was induced in freshly isolated or culture-expanded Sca-1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells isolated from SM of C57BL/6 mice. Expression of mRNA of cardiac-specific antigens and those associated with pluripotency was examined by real-time RT-PCR. Phenotypic analysis of expanded cells was performed during each passage by flow cytometry. Cardiomyocytic differentiation in vitro was verified by morphologic analysis, immunocytochemistry, and contractile properties. In freshly isolated cells, compared with unfractionated SM-derived cells as well as SM+ cells, mRNA expression of cardiac-specific antigens and those associated with cellular pluripotency was greater in SM- cells. Compared with SM- cells, SM+ cells exhibited greater expansion capacity. Freshly isolated SM- cells exhibited greater cardiac differentiation potential compared with freshly isolated SM+ cells (21.8 ± 0.3% of SM- cells positive for cardiac markers vs. 9.1 ± 0.7% of SM+ cells, P = 0.00009). Differentiated SM- cells acquired a cardiomyocytic phenotype and exhibited spontaneous rhythmic contractions in vitro. The number of Sca-1+ cells in the SM- population increased markedly with time (0.9 ± 0.1% in freshly isolated cells vs. 11.9 ± 0.9% after the first passage vs. 99.0 ± 0.6% after the second passage). This increase in Sca-1 expression was associated with a marked decline in the expression of cardiac markers following differentiation induction in culture-expanded SM- cells (21.8 ± 0.3% in unexpanded cells vs. 16.6 ± 1.3% after the first passage vs. 6.0 ± 0.5% after the second passage, P = 0.00001 vs. unexpanded cells). In contrast, the SM+ cells did not exhibit any consistent pattern in either phenotypic or differentiation capability with expansion. We conclude that SM- cells are inherently predisposed to undergo cardiac differentiation and are enriched in markers of pluripotency. While both Sca-1+ and Sca-1- primitive cells from SM can undergo cardiac differentiation, Sca-1- cells exhibit greater cardiomyogenic potential, and the appearance of Sca-1 during expansion is associated with a decline in cardiac differentiation plasticity.

KW - Cardiac regeneration

KW - Cardiomyocyte differentiation

KW - Pluripotency

KW - Sca-1

KW - Skeletal muscle

KW - Stem cells

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