Cdks and cyclins link G1 length and differentiation of embryonic, neural and hematopoietic stem cells

It is long known that stem cell differentiation correlates with a lengthening of the cell cycle, in particular G(1). Moreover, models were proposed for mammalian embryonic, neural and hematopoietic stem cells whereby lengthening of G(1) is a cause, rather than a consequence, of differentiation. These models are based on the concept that time, i.e.,: G(1) length, may be a limiting factor for cell fate change to occur because differentiation factors require time in order to trigger a physiological response. Despite the many correlative studies, this hypothesis proved difficult to demonstrate because most trophic, signaling or transcription factors involved in stem cell differentiation may concurrently, but independently, also have an effect on cell cycle progression, which calls for a thorough review on the differentiation role of genes whose best characterized and long established function is exclusively to control G(1). For this reason, we here focus our attention on the effects that the core molecular machinery controlling G(1) progression, i.e.,: the G(1)-specific cyclin dependent kinase (cdk)/cyclin complexes, have on stem cell differentiation. In particular, we will discuss the effects of G(1)-cdks/cyclins on differentiation of embryonic, neural and hematopoietic stem cells during development and adulthood, for which a role of G(1) length has been proposed.