Table 1.

Hallmarks of CM Maturation.

Phenotype	Immature (late fetal)	Mature (Adult)	PSC-CMs	Regulators	References
Cell Size	small	large	small	GATA4/6	^{185, 210}
Cell Shape	In situ: rod-shaped (4:1::L:W); cultured: stellate	In situ and dissociated: rod-shaped (7:1::L:W)	irregular/round	ECM composition and patterning, mechanical load, ERK1/2 signaling	^{184, 186, 190, 224}
Sarcomere Alignment	organized	superbly organized	disorganized	cell shape, mechanical load, substrate stiffness	^{190, 216, 217}
Sarcomere Components	TNNI1, MYH7, TTN-N2BA, EH-MYOM1,TNNT2 exon 5 inclusion	TNNI3, MYH6, TTN-N2B, TNNT2 exon 5 exclusion	variable	Thyroid hormone; maturation related transcriptional programs are currently not well understood	^{191–195, 221}
Metabolism	glycolysis	oxidative phosphorylation	Glycolysis	PPAR signaling, greater oxygen availability after birth	^{200, 205, 208}
Mitochondria	low number, small and round	high number, large and ovoid, close proximity to myofibers	ovoid, clustered around nucleus and cell periphery	AMPK, PPAR signaling, Mitofusins 1 and 2	^201–203
Proliferative Capacity	high	very low	can proliferate for ~1month after contraction begins	NRG1/ERBB2/4, YAP/TEAD, IGF2/IGF1R/PI3K/ERK, BMP10, WNT/β-catenin, NOTCH	^{101, 103, 110, 115, 116, 159}
Nucleus	mononucleated	multinucleated or polyploid	mononucleated	Proliferation regulators above	^{101, 103, 110, 115, 116, 159}
T-Tubules	none	extensive network	none	JPH2, BIN1	^{198, 199}