Jaba Tkemaladze
Asymmetric stem cell division (ASCD) is a fundamental process for generating cellular diversity while maintaining the stem cell pool. This review synthesizes evidence from diverse model systems to establish a paradigm-shifting hypothesis: centrioles are not passive microtubule-organizing centers but active determinants that orchestrate ASCD. We argue that centrioles function as integrative hub-organelles, executing four coordinated roles: as a Compass that fixes the division axis via cortical linkages, a Dispatcher that asymmetrically recruits and segregates fate determinants, a Sensor that transduces niche signals through the primary cilium, and a Chronometer that regulates division timing. The molecular asymmetry between the mother and daughter centriole, established during interphase, is a prerequisite for correct spindle orientation and asymmetric cargo partitioning. Disruption of centriolar integrity, as seen in human "centriolopathies" like primary microcephaly and ciliopathies, leads to randomized divisions and tissue malformation. Conversely, in cancer, centrosome amplification disrupts this intrinsic asymmetry, promoting symmetric, expansive divisions of stem-like cells. This integrative model positions the centriole as the central architect of cell fate, translating extrinsic polarity into intrinsic asymmetry. Understanding this centriole-centric program opens novel avenues in regenerative medicine, by controlling differentiation in vitro, and in oncology, by targeting the self-renewal of cancer stem cells.