Research

Our current research projects are focused on understanding the causes and consequences of aneuploidy during human development. We use human pluripotent stem cells and a multi-disciplinary approach to investigate aneuploidy in development.

1. Identifying the Mitotic Pathways Responsible for Chromosome Segregation Errors in hPSCs

Image of an H1 hPSCs with a lagging chromosome in anaphase (image by C. Deng).
Image of an H1 hPSCs with a lagging chromosome in anaphase (image by C. Deng).
Surprisingly, previous studies show that mitotic chromosome segregation errors are more common in human preimplantation totipotent and pluripotent embryonic cells than meiotic errors. Yet, we do not understand the mechanisms responsible for mitotic chromosome segregation errors during development. 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 these errors and exploring the association between mitotic errors and developmental potential.

2. Investigating How the Cell Cycle Structure of hPSCs Influences their Response to Chromosome Segregation Errors

Previous studies show that following a chromosome segregation error in mitosis, somatic cells often respond in the subsequent G1 and initiate cell cycle arrest to prevent the propagation of aneuploid cells. However, G1 has a significantly shorter duration in hPSCs (~2.5-3 hrs) compared to somatic cells (~10 hrs). We are investigating how the distinct G1 cell cycle structure of hPSCs influences their response to chromosome segregation errors.

Cell cycle duration in hPSCs and somatic cells.
Cell cycle duration in hPSCs and somatic cells.
Time-lapse live cell movie of an H1 hPSC expressing H2B-GFP (green) and a G1 reporter (magenta). Following mitosis, the G1 reporter turns on and off. White arrows indicate the two daughter cells (movie by C. Deng).

3. Exploring How Aneuploidy Impacts Embryonic Tissue Formation

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 fertilization (IVF) human embryos can lead to normal development but how this occurs is unknown. We are investigating the impact of aneuploidy on embryonic tissue formation to better understand how genome stability is eventually achieved to support normal development.

An example of a mosaic IVF preimplantation embryo composed of diploid and aneuploid embryonic cells (adapted from Mertzanidou et al, 2013).
An example of a mosaic IVF preimplantation embryo composed of diploid and aneuploid embryonic cells (adapted from Mertzanidou et al, 2013).
Fluorescent in-situ hybridization of hPSCs with a probe for chromosome 17 (magenta) showing that the population is a mix of diploid and aneuploid cells (image A. Ya).
Fluorescent in-situ hybridization of hPSCs with a probe for chromosome 17 (magenta) showing that the population is a mix of diploid and aneuploid cells (image A. Ya).