It is well-known that embryonic stem cells has faster cell cycle (very roughly about 12 hours), while typically normal cells has a much longer cell cycle (very roughly about 24 hours). Of course, it is not only the duration is different, but there are tons of papers describing differences between cell cycle regulation for normal vs ESC.
Question: What is known about "switch" mechanisms from the fast cell cycle to normal cell cycle ? (During/after differentiation happens.) Any references, ideas, comments are welcome.
For some cancer cell lines in our research we see that certain drugs can switch from "fast" to "normal" cell cycle patterns - we want to understand the mechanisms how that can happen. Any comments about that are also welcome.
The duration of the cell cycle is variable between different types of
stem cells. ESCs have a shorter cell cycle compared to somatic stem
cells, which is due to a significantly abbreviated G1 phase and a
prolonged S phase [39,40,41]. Previous studies have explored the
phosphorylation status of pRb as a regulator for the length of G1
phase. Since mESCs lack cyclin D-CDK4 as well as cyclin E-CDK2, pRb
will not be phosphorylated and thereby not stimulating the cyclin
E-CDK2 activity [42]. Therefore, the time spent in G1 phase compared
to S phase may be a key feature of the pluripotency fate [12].
Moreover, DNA damage response pathways, which are activated in the G1
phase, are reduced or absent in both hESCs and mESCs [43]. Several
negative regulators of cell cycle progression, including p53,
p16/INK4A, p19/ARF and p21/Cip1, are expressed at low levels in ESCs,
while DNA repair and replication regulators are expressed at high
levels [6, 43].
You don't specify which anti-cancer drugs you are talking about, but for example, DNA methylation inhibitors like 5-Azacytidine and 5-aza-2’-deoxycytidine cause a viable DNA damage stress response by stalling the replication fork and for inhibitors of the Cyclin dependent kinases (CDKs), the mode of action is evident ;-)
Thanks Matthias that is very helpful. That paper is in my reading list, but quite far, so I should "switch" its position and should look in it now )))) Still it is not clear mechanisms of "switch", but indeed gives a clue what may happen.
Thanks Matthias that is very helpful. That paper is in my reading list, but quite far, so I should "switch" its position and should look in it now )))) Still it is not clear mechanisms of "switch", but indeed gives a clue what may happen.