Alex K Chen Posted October 5, 2023 Report Share Posted October 5, 2023 (edited) Aged apolar HSCs undergo preferentially self-renewing symmetric divisions, resulting in daughter stem cells with reduced regenerative capacity and lymphoid potential, while young polar HSCs undergo preferentially asymmetric divisions.Sep 20, 2018 Aging alters the epigenetic asymmetry of HSC division - PLOS PLOS https://journals.plos.org › plosbiology › article › journal.... https://www.fightaging.org/archives/2015/09/failure-of-asymmetric-cell-division-mechanisms-may-contribute-to-stem-cell-aging/ ==== Denis Odinokov Favorites · · Hypothesis: individuals with symmetrical kinetochores in both maternal and paternal chromatids may experience longer lifespans due to a slower rate of stem cell pool exhaustion, which is caused by fewer chromosomal abnormalities during cell division. Comments Andrei Beloveshkin · Cool Reply 2d Denis Odinokov Andrei Beloveshkin я сам до сих пор в шоке )) Reply See translation 2d Lev Yampolsky please clarify. What are symmetrical kinetochores? And what are maternal and paternal chromosome _pairs_? Reply 2d Denis Odinokov Lev Yampolsky yep, the word pairs is redundant, thanks Reply 2d Denis Odinokov Lev Yampolsky let me paraphrase the hypothesis. The locations of kinetochores on maternal and paternal chromosomes may not be symmetrical, which could lead to distortion during cell division, thereby increasing the likelihood of chromosomal abnormalities. These abnormalities may subsequently lead to apoptosis. This hypothesis was inspired by unpunished data on the origin of Down syndrome. Reply 2d Lev Yampolsky during mitosis maternal and paternal chromosomes are handled completely independently, why would different location of kinetochores matter? Reply 2d Edited Lev Yampolsky of course the story about origin of Down syndrome is different, as most of non-disjunctions leading to trisomies occur in meiosis. Reply 2d Denis Odinokov Lev Yampolsky Down syndrome can result not only from meiotic but also from mitotic catastrophes, and in rare cases, it can even be rescued by the placenta, which results in a healthy fetus and trisomic placenta. Reply 2d Edited Denis Odinokov Lev Yampolsky thank you for helping me think through it Reply 2d Lev Yampolsky does not answer my skepticism - depletion of stem cells obviously occurs through errors in mitosis; what role differences between paternal and maternal chromosomes can play in that? Reply 2d Denis Odinokov Lev Yampolsky I need to read more papers to answer your question. Planning to start with https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509025/ https://www.sciencedirect.com/.../pii/S2211124717310768 NCBI.NLM.NIH.GOV Transient defects of mitotic spindle geometry and chromosome segregation errors Transient defects of mitotic spindle geometry and chromosome segregation errors Reply 2d Cosmo Mielke I found an important gene in Horvath's original clock that regulates kinetichors.... I need to finish that analysis Reply 2d Denis Odinokov Cosmo Mielke My hypothesis is that asymmetrical kinetochores of chromatids lead to premature stem cell pool exhaustion. To validate it, I need access to PacBio haplotype-phased long-read data of centromeres, which captures methylation marks. The region exhibiting low methylation is likely to be a kinetochore. Reply 2d Cosmo Mielke Denis Odinokov is there a mechanistic tie between kinetichor asymmetry and centriole number? Reply 1d Denis Odinokov Cosmo Mielke it's a very good question! There could be some linkage as both phenomena are presumably involved in the missegregation of chromosomes and aneuploidy. Reply 1d Yi Peke По этой гипотезе - инбридинг может иной раз и увеличивать ПЖ. Reply See translation 1d Denis Odinokov Yi Peke к сожалению, гомозиготы менее жизнеспособны, чтобы инбридинг сработал для увеличения ПЖ Reply See translation 1d Edited Alex K. Chen Isn't asymmetric cell division important for preserving stemness? Reply 21h Denis Odinokov Alex K. Chen slightly asymmetric kinetochores should not affect stem cell division per se yet hypothetically might increase the likelihood of chromosomal abnormalities. BTW, I wonder if stem cell aging is driven by kinetochore asymmetry - about 90 percent of age-related aneuploidies are explained by weakened centromere cohesion. Reply 18h Edited Edited October 5, 2023 by InquilineKea Quote Link to comment Share on other sites More sharing options...
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