A novel pathway controls stem-cell proliferation independently from differentiation

The ability of stem cells to self-renew depends, among other things, on their ability to divide. However, the typical mechanism that controls cellular proliferation — the G1 checkpoint — is associated with differentiation in stem cells. How can stem cells proliferate without losing multipotency? Reporting in Nature, Patrik Ernfors of the Karolinska Institutet in Sweden and colleagues show that proliferation is controlled in some stem cells during the DNA synthesis phase, or S phase, rather than during the G1 phase.

The authors initially observed that embryonic stem (ES) cells possess functional -aminobutyric acid A receptors (GABAARs), Treating these cells with the GABAAR-specific agonist muscimol reduced the number of stem cells in culture by causing the accumulation of cells in S phase (and thereby preventing cells from undergoing cell division). While fewer in number, treated cells could differentiate normally.ancer.