Calcium Dependent CAMTA1 in Adult Stem Cell Commitment to a Myocardial Lineage
Muller-Borer, Barbara; Esch, Gwyn; Aldina, Rob; Woon, Woohyun; Fox, Raymond; Bursac, Nenad; Hiller, Sylvia; Maeda, Nobuyuo; Shepherd, Neal; Jin, Jian Ping; Hutson, Mary; Anderson, Page A. W.; Kirby, Margaret L.; Malouf, Nadia N.
The phenotype of somatic cells has recently been found to be reversible. Direct reprogramming of one cell type into another has been achieved with transduction and over expression of exogenous defined transcription factors emphasizing their role in specifying cell fate. To discover early and novel endogenous transcription factors that may have a role in adult-derived stem cell acquisition of a cardiomyocyte phenotype, mesenchymal stem cells from human and mouse bone marrow and rat liver were co-cultured with neonatal cardiomyocytes as an in vitro cardiogenic microenvironment. Cell-cell communications develop between the two cell types as early as 24 hrs in co-culture and are required for elaboration of a myocardial phenotype in the stem cells 8-16 days later. These intercellular communications are associated with novel Ca(2+) oscillations in the stem cells that are synchronous with the Ca(2+) transients in adjacent cardiomyocytes and are detected in the stem cells as early as 24-48 hrs in co-culture. Early and significant up-regulation of Ca(2+)-dependent effectors, CAMTA1 and RCAN1 ensues before a myocardial program is activated. CAMTA1 loss-of-function minimizes the activation of the cardiac gene program in the stem cells. While the expression of RCAN1 suggests involvement of the well-characterized calcineurin-NFAT pathway as a response to a Ca(2+) signal, the CAMTA1 up-regulated expression as a response to such a signal in the stem cells was unknown. Cell-cell communications between the stem cells and adjacent cardiomyocytes induce Ca(2+) signals that activate a myocardial gene program in the stem cells via a novel and early Ca(2+)-dependent intermediate, up-regulation of CAMTA1.
Muller-Borer, Barbara, & Esch, Gwyn, & Aldina, Rob, & Woon, Woohyun, & Fox, Raymond, & Bursac, Nenad, & Hiller, Sylvia, & Maeda, Nobuyuo, & Shepherd, Neal, & Jin, Jian Ping, & Hutson, Mary, & Anderson, Page A. W., & Kirby, Margaret L., & Malouf, Nadia N.. (January 2012). Calcium Dependent CAMTA1 in Adult Stem Cell Commitment to a Myocardial Lineage. PLoS ONE, 7(6), 1- 12. Retrieved from http://hdl.handle.net/10342/5425
Muller-Borer, Barbara, and Esch, Gwyn, and Aldina, Rob, and Woon, Woohyun, and Fox, Raymond, and Bursac, Nenad, and Hiller, Sylvia, and Maeda, Nobuyuo, and Shepherd, Neal, and Jin, Jian Ping, and Hutson, Mary, and Anderson, Page A. W., and Kirby, Margaret L., and Malouf, Nadia N.. "Calcium Dependent CAMTA1 in Adult Stem Cell Commitment to a Myocardial Lineage". PLoS ONE. 7:6. (1-12), January 2012. December 15, 2018. http://hdl.handle.net/10342/5425.
Muller-Borer, Barbara and Esch, Gwyn and Aldina, Rob and Woon, Woohyun and Fox, Raymond and Bursac, Nenad and Hiller, Sylvia and Maeda, Nobuyuo and Shepherd, Neal and Jin, Jian Ping and Hutson, Mary and Anderson, Page A. W. and Kirby, Margaret L. and Malouf, Nadia N., "Calcium Dependent CAMTA1 in Adult Stem Cell Commitment to a Myocardial Lineage," PLoS ONE 7, no. 6 (January 2012), http://hdl.handle.net/10342/5425 (accessed December 15, 2018).
Muller-Borer, Barbara, Esch, Gwyn, Aldina, Rob, Woon, Woohyun, Fox, Raymond, Bursac, Nenad, Hiller, Sylvia, Maeda, Nobuyuo, Shepherd, Neal, Jin, Jian Ping, Hutson, Mary, Anderson, Page A. W., Kirby, Margaret L., Malouf, Nadia N.. Calcium Dependent CAMTA1 in Adult Stem Cell Commitment to a Myocardial Lineage. PLoS ONE. January 2012; 7(6): 1-12. http://hdl.handle.net/10342/5425. Accessed December 15, 2018.