Our current research projects focus on understanding the causes and consequences of aneuploidy during human development using human pluripotent stem cells and multi-disciplinary approaches.
1. Identifying the Mitotic Pathways Causing Chromosome Segregation Errors in hPSCs
Surprisingly, studies show that mitotic chromosome segregation errors are common in human preimplantation embryonic cells and human pluripotent stem cells (hPSCs). Yet, we do not understand the mechanisms responsible for these mitotic errors. We discovered that the most common mitotic error in hPSCs is lagging chromosomes in anaphase due to improper chromosome microtubule attachments. Ongoing research efforts are directed at dissecting the molecular pathways in hPSCs that cause mitotic errors and exploring the association between chromosome segregation fidelity and developmental potential.
2. Investigating the Response of hPSCs to Chromosome Segregation Errors
Research shows that following a chromosome segregation error in mitosis, somatic cells fail to proliferate and initiate cell cycle arrest in the subsequent G1 phase. In contrast, we discovered that hPSCs tolerate being aneuploid and proliferate with abnormal genomes. G1 duration is significantly shorter in hPSCs (~2.5-3 hrs) compared to somatic cells (~10 hrs), so we are investigating how the distinct G1 cell cycle structure of hPSCs influences their response to chromosome segregation errors.
3. Exploring How Aneuploidy Impacts Embryonic Development
A consequence of mitotic errors in human preimplantation embryonic cells is the formation of mosaic human embryos composed of diploid and aneuploid cells. Recent studies show that mosaic in vitro fertilized human embryos can lead to normal development but how this occurs is unknown. In mosaic populations of aneuploid and diploid hPSCs, we find that cell non-autonomous competition eliminates less fit aneuploid cells. Ongoing research efforts are aimed at investigating how aneuploidy causes cell competition to better understand how genome stability may eventually be achieved to support normal human development.
