Table.

Hallmarks of Cardiomyocyte Maturation

PhenotypeImmature (Late Fetal)Mature (Adult)PSC-CMsRegulatorsReferences
Cell sizeSmallLargeSmallGATA4/6183,208
Cell shapeIn situ: rod-shaped (4:1::L:W); cultured: stellateIn situ and dissociated: rod-shaped (7:1::L:W)Irregular/roundECM composition and patterning, mechanical load, ERK1/2 signaling182,184,188,222
Sarcomere alignmentOrganizedSuperbly organizedDisorganizedCell shape, mechanical load, substrate stiffness188,214,215
Sarcomere componentsTNNI1, MYH7, TTN-N2BA, EH-MYOM1,TNNT2 exon 5 inclusionTNNI3, Myh6, TTN-N2B, TNNT2 exon 5 exclusionVariableThyroid hormone; maturation-related transcriptional programs are currently not well understood189193,219
MetabolismGlycolysisOxidative phosphorylationGlycolysisPPAR signaling, greater oxygen availability after birth198,203,206
MitochondriaLow number, small and roundHigh number, large and ovoid, close proximity to myofibersOvoid, clustered around nucleus and cell peripheryAMPK, PPAR signaling, mitofusins 1 and 2199201
Proliferative capacityHighVery lowCan proliferate for ≈1 mo after contraction beginsNRG1/ERBB2/4, YAP/TEAD, IGF2/IGF1R/PI3K/ERK, BMP10, WNT/β-catenin, NOTCH100,102,108,113,114,158
NucleusMononucleatedMultinucleated or polyploidMononucleatedProliferation regulators above100,102,108,113,114,158
T-tubulesNoneExtensive networkNoneJPH2, BIN1196,197
  • PPAR indicates peroxisome proliferator-activated receptor; and PSC-CM, pluripotent stem cell–derived cardiomyocyte.