FUNCTIONAL CHARACTERIZATION OF PUTATIVE MITOTIC BOOKMARKING FACTORS IN PLURIPOTENCY MAINTENANCE

Abstract

Pluripotent stem cells are a special population of stem cell with indefinitely self-renewal and unlimited differentiation capability, which makes them an attractive avenue for regenerative medicine and disease modeling. Therefore, it is important to understanding the fundamental mechanisms that govern and maintain their pluripotent state. A phenomenon termed mitotic bookmarking has recently been suggested as a potential mechanism involved in the stable propagation of cellular identity through the cell cycles. Candidate-based studies have identified mitotic bookmarking factors that are retained on the mitotic chromatin and preserve the transcriptional memory of the cell. Nevertheless, there is a poor understanding of which proteins can serve as mitotic bookmarks, as well as the chromatin dynamics of bookmarked sites during mitosis and the start of the G1 phase. We have previously identified a list of putative mitotic bookmarking factors in pluripotent stem cells, from which we tested the role of PARP1, HDGF, and PSIP1 as potential bookmarks for the propagation of the pluripotent state through mitosis. Here we showed that the absence of PARP1 at the M-G1 transition impairs self-renewal capability of pluripotent stem cells without affecting the proliferation and cell cycle progression. Conclusive evidence that establishes a role for HDGF or PSIP1 in mitotic bookmarking of pluripotent stem cells has yet to emerge. However, our work provides a new avenue for exploring the functional importance of mitotic bookmarks in pluripotent maintenance.