There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the "fetal" TNNI gene, TNNI1 (ssTnI), together in temporal concert with its stoichiometric replacement by the adult TNNI gene product, TNNI3 (cTnI), represents a quantifiable ratiometric maturation signature. We examined the TNNI isoform transition in human induced pluripotent stem cell (iPSC) cardiac myocytes (hiPSC-CMs) and found the fetal TNNI signature, even during long-term culture. Rodent stem cell-derived and primary myocytes, however, transitioned to the adult TnI profile. Acute genetic engineering of hiPSC-CMs enabled a rapid conversion toward the mature TnI profile. While there is no single marker to denote the mature cardiac myocyte, we propose that tracking the cTnI:ssTnI protein isoform ratio provides a valuable maturation signature to quantify myocyte maturation status across laboratories.
Bibliographical noteFunding Information:
We thank Dr. Joseph C. Wu (Stanford University) for providing some additional hiPSC-CMs for our study and Mr. Chris Chapman for his assistance. This work is supported by NIH PCBC U01 HL1000407 and HL099773 (D.J.G., T.J.K., J.Z., M.K., J.M.M., and J.C.W.), NIH R01 (J.M.M.), and R24 HL117756 (J.C.W.). We acknowledge support from the Lillihei Heart Institute to this study. T.J.K. is a founding shareholder and consultant for Cellular Dynamics International.
© 2014 The Authors.