Higher cardiogenic potential of iPSCs derived from cardiac versus skin stromal cells

Abstract

Prior studies have demonstrated that founder cell type could influence induced pluripotent stem cells (iPSCs) molecular and developmental properties at early passages after establishing their pluripotent state. Herein, we evaluated the persistence of a functional memory related to the tissue of origin in iPSCs from syngeneic cardiac (CStC) vs skin stromal cells (SStCs). We found that, at passages greater than 15, iPSCs from cardiac stromal cells (C-iPSCs) produced a higher number of beating embryoid bodies than iPSCs from skin stromal cells (S-iPSCs). Flow cytometry analysis revealed that dissected beating areas from C-iPSCs exhibited more Troponin-T positive cells compared to S-iPSCs. Beating areas derived from C-iPSCs displayed higher expression of cardiac markers, more hyperpolarized diastolic potentials, larger action potential amplitude and higher contractility than beaters from skin. Also, different microRNA subsets were differentially modulated in CStCs vs SStCs during the reprogramming process, potentially accounting for the higher cardiogenic potentials of C-iPSCs vs S-iPSCs. Therefore, the present work supports the existence of a founder organ memory in iPSCs obtained from the stromal component of the origin tissue.

Patient-specific primary and pluripotent stem cell-derived stromal cells recapitulate key aspects of arrhythmogenic cardiomyopathy

“…We speculate that higher expression of desmosomal genes in hiPSC-D cells might be related to their tissue of origin, as hiPSCs were generated from skin fibroblast biopsy. Since the skin is one of the organs with the most abundant desmosomes, we hypothesize that hiPSC-D cells might retain a certain epigenetic memory of the material source 25 . In addition, a lower expression, even if not statistically significant, was confirmed for PKP2 in the ACM lines of both cell types, thus corroborating one of the characteristics of ACM stromal cells 6 , 12 .…”

Model of Murine Ventricular Cardiac Tissue for In Vitro Kinematic-Dynamic Studies of Electromagnetic and β-Adrenergic Stimulation

“…By an algorithm based on the Matlab programming language (The MathWorks Inc., Natick, MA), frame by frame and for each marker, we have studied the kinematics and the dynamics of the beating cardiac syncytia, as previously described [ 25 , 26 , 34 ] (see Appendix below for the mathematical details). In particular, in this work, we have evaluated the syncytium contraction in terms of maximum contraction displacement [pixel], contractility (maximum contraction velocity) [pixel/s], and contraction acceleration [pixel/s 2 ].…”