Table 1.

Molecular differences in cell cycle control among ESCs, lineage committed cells, and iPSCs.

	ESCs	Lineage Committed Cells	iPS Cells	References
Cell Cycle Length	Mice: 10 h	24-32 h	16-18 h	1, 2, 7, 13, 15
	Humans: 15-16 h
G1 Length	Mice: 1 – 2 h	8-12 h	2-3 h	1, 2, 7, 10
	Human: 2.5 -3 h
CDK Activity	Most CDKs are active throughout the cell cycle, as a consequence of the relatively stable levels of cyclins, and the absence (or very low expression) of CDKIs.	Periodic activation of CDKs, during the cell cycle. This is regulated by expression of CDKs and by cyclins and CDKIs.	Cell cycle-dependent expression of cyclin E and cyclin B1.	1, 2, 3, 5, 6, 7, 9, 10, 11, 12, 14
	Very high expression of CDK2.	CDK activity is counteracted by CDKIs, p15, p16, p18, p19, p21, p27 and p57.	Constitutively high levels of CDK2.
	In mice, cyclins D1, D3, E and A2 are expressed at comparable levels throughout the cell cycle.		Cyclin D1 levels are higher than in ESCs. Down-regulation of cyclin E1/D2 decreases the efficiency of reprogramming.
	The CDK4/cyclin D complex is not present in mouse,		Down-regulation of CDK2, CDK4, or cyclin D1 does not affect reprogramming efficiency.
	CDKIs, p16, p21, p27, and p57 are silenced or expressed at very low levels.		Overexpression of p15, p16, or p21 blocks reprogramming.
	Some genes show cell cycle dependent expression: CDC25a, cyclin E, cyclin D2, CDK4, CDK6, cyclin A, c-Myc, CDK1, and cyclin B1.		Overexpression of cyclin D1, D2, or E2, increases reprogramming efficiency.
Check Points	Lack normal somatic cell cycle checkpoint controls at the G1/S transition.	Strong cell cycle checkpoints in G1 and G2.	Lack normal somatic cell cycle checkpoint controls in the G1/S transition.	5,10,14, 16, 18
	After exposure to radiation, cells arrest in G2 Following activation of the ATM-dependent checkpoint signaling cascade, double stranded breaks are repaired.		After exposure radiation, cells arrest in G2. Following activation of the ATM-dependent checkpoint signaling cascade, double stranded breaks are repaired.
G1/S Transition	Exogenous growth factor independent.	Exogenous growth factor dependent.	Exogenous growth factor independent.	1, 4, 5, 6, 7, 8, 10, 14, 15, 17, 19
	Independent of the pRB/E2F switch at R point.	Dependent on the pRb/E2F switch and c-Myc at R-point	Down-regulation of pRb increases the efficiency of reprogramming.
	Hinf-P/NPAT dependent (S-point).	Hinf-P/NPAT dependent (S-point).	Hinf-P/NPAT dependent (S-point).
	Insensitive to cyclin D/CDK regulation and to the CDK inhibitor, p16Ink4a.	Sensitive to cyclin D/CDK regulation and to the CDK inhibitor, p16Ink4a.	ND: Insensitive to CDK regulation.
	p53 does not induce G1 arrest in response to DNA damage.	p53-dependent cell cycle arrest in response to DNA damage.	p53-dependent cell cycle arrest in G1/S, mediated by p21, leads to senescence, which inhibits reprogramming.
Nuclear Structure	NAPT foci double prior to the onset of S phase.	NAPT foci double only upon entry into S phase.	NAPT foci double prior to the onset of S phase.	2, 19

DSB: Double strand breaks; ND: Not directly experimentally validated. However, evidence suggests this is likely the case. iPS cells: inducible pluripotent stem cells

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