A pluripotent developmental state confers a low fidelity of chromosome segregation.

ABSTRACT: During in vitro propagation, human pluripotent stem cells (hPSCs) frequently become aneuploid with incorrect chromosome numbers due to mitotic chromosome segregation errors. Yet, it is not understood why hPSCs exhibit a low mitotic fidelity. Here, we investigate the mechanisms responsible for mitotic errors in hPSCs and show that the primary cause is lagging chromosomes in anaphase with improper merotelic microtubule attachments. Accordingly, short-term treatment (<24 h) with small molecules that prolong mitotic duration or destabilize chromosome microtubule attachments reduces merotelic errors and lagging chromosome rates, although hPSCs adapt and lagging chromosome rates rebound upon long-term (>24 h) microtubule destabilization. Strikingly, we also demonstrate that mitotic error rates c

SUBMITTER: Deng C 

PROVIDER: S-EPMC9968987 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature