Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells
Author
Muller-Borer, Barbara J.; Cascio, Wayne E.; Esch, Gwyn L.; Kim, Hyung-Suk; Coleman, William B.; Grisham, Joe W.; Anderson, Page A. W.; Malouf, Nadia N.
Abstract
The mechanisms underlying stem cell acquisition of a cardiac
phenotype are unresolved. We studied early events during the
acquisition of a cardiac phenotype by a cloned adult liver stem cell
line (WB F344) in a cardiac microenvironment. WB F344 cells express a priori the transcription factors GATA4 and SRF, connexin 43 in the cell membrane, and myoinositol 1,4,5-triphosphate receptor in the perinuclear region. Functional cell– cell communication developed between WB F344 cells and adjacent cocultured cardiomyocytes in 24 h. De novo cytoplasmic [Ca2 +]c and nuclear [Ca2+ ]nu oscillations appeared in WB F344 cells, synchronous with [Ca2+ ]i transients in adjacent cardiomyocytes. The [Ca2 +] oscillations in the WB F344 cells, but not those in the cardiomyocytes, were eliminated by a gap junction uncoupler and reappeared with its removal. By 24 h, WB F344 cells began expressing the cardiac transcription factors Nkx2.5, Tbx5, and cofactor myocardin; cardiac proteins 24 h later; and a sarcomeric pattern 4–6 days later. Myoinositol 1,4,5-triphosphate receptor inhibition suppressed WB F344 cell [Ca2 +]nu oscillations but not [Ca2+ ]c oscillations, and L-type calcium channel inhibition eliminated [Ca2 +] oscillations in cardiomyocytes and WB F344 cells. The use of these inhibitors was associated with a decrease in Nkx2.5, Tbx5, and myocardin expression in the WB F344 cells. Our findings suggest that signals from cardiomyocytes diffuse through shared channels, inducing [Ca2 +] oscillations in the WB F344 cells. We hypothesize that the WB F344 cell [Ca2 +]nu oscillations activate the expression of a cardiac specifying gene program, ushering in a cardiac phenotype. Originally published Proc Natl Acad Sci, Vol. 104, No. 10, March 2007
Date
2007-03-06
Citation:
APA:
Muller-Borer, Barbara J., & Cascio, Wayne E., & Esch, Gwyn L., & Kim, Hyung-Suk, & Coleman, William B., & Grisham, Joe W., & Anderson, Page A. W., & Malouf, Nadia N.. (March 2007).
Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells.
Proceedings of the National Academy of Sciences,
104(10),
3877-
3882. Retrieved from
http://hdl.handle.net/10342/3060
MLA:
Muller-Borer, Barbara J., and Cascio, Wayne E., and Esch, Gwyn L., and Kim, Hyung-Suk, and Coleman, William B., and Grisham, Joe W., and Anderson, Page A. W., and Malouf, Nadia N..
"Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells". Proceedings of the National Academy of Sciences.
104:10. (3877-3882),
March 2007.
December 08, 2023.
http://hdl.handle.net/10342/3060.
Chicago:
Muller-Borer, Barbara J. and Cascio, Wayne E. and Esch, Gwyn L. and Kim, Hyung-Suk and Coleman, William B. and Grisham, Joe W. and Anderson, Page A. W. and Malouf, Nadia N.,
"Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells," Proceedings of the National Academy of Sciences 104, no.
10 (March 2007),
http://hdl.handle.net/10342/3060 (accessed
December 08, 2023).
AMA:
Muller-Borer, Barbara J., Cascio, Wayne E., Esch, Gwyn L., Kim, Hyung-Suk, Coleman, William B., Grisham, Joe W., Anderson, Page A. W., Malouf, Nadia N..
Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells. Proceedings of the National Academy of Sciences.
March 2007;
104(10):
3877-3882.
http://hdl.handle.net/10342/3060. Accessed
December 08, 2023.
Collections
Publisher
East Carolina University