讲座时间：16:30 — 17:30
题目：Breaking symmetry -- Asymmetric epigenetic inheritance during Drosophila germline stem cell asymmetric division
The Johns Hopkins University
Many types of stem cells undergo asymmetric cell divisions to give rise to daughter cells with distinct cell fates: one that retains stem cell identity and another that differentiates. During asymmetric cell division, the genomic information is preserved through DNA replication followed by equal partition to the two daughter cells. A long-standing question has been how the epigenetic information of a stem cell is transferred to the daughter cells. Using the Drosophila male germline stem cell lineage, our recent studies showed that epigenetic information is inherited asymmetrically during asymmetric stem cell divisions. We have proposed a two-step model to explain asymmetric epigenetic inheritance. (1) Prior to mitosis, preexisting and newly synthesized histones are differentially distributed on the two sets of sister chromatids. (2) During mitosis, the set of sister chromatids containing preexisting histones is segregated to the stem cell, while the set of sister chromatids enriched with newly synthesized histones is segregated to the other daughter cell that differentiates.
In order to explore a potential role for DNA replication in patterning epigenetic inheritance, we have taken an imaging-based approach to visualize DNA replication in Drosophila male germline. We have used superresolution microscopy and found that new histones and old histones show distinct spatial separation both at the replication fork and on newly replicated sister chromatids. These studies further suggest that newly synthesized histones preferentially associate with the lagging-strand during progression of the replication fork. Based on these data, we propose that the asymmetries inherent to the process of DNA replication serve to bias histone inheritance such that the leading strand preferentially inherits mostly old histone, whereas the lagging strand inherits predominantly newly synthesized histones. Our ongoing research is to elucidate how stem cells maintain their epigenetic memory through many divisions and whether the loss of stem cell epigenetic memory leads to diseases.
1. Tran, V.*, Lim, C.*, Xie, J. and Chen, X. (2012) Asymmetric division of Drosophila male germline stem cell shows asymmetric histone distribution. Science, 338(6107): 679-682, PMCID: PMC3532436 (* equal contribution).
2. Tran, V.*, Feng, L.J.* and Chen, X. (2013) Asymmetric distribution of histones during Drosophila male germline stem cell asymmetric divisions. Invited review to Chromosome Research, 21:255-269. PMCID: PMC4008969. (* equal contribution)
3. Xie, J., Wooten, M., Tran, V., Chen, B-C., Pozmanter, C., Simbolon, C., Betzig, E. and Chen, X. (2015) Histone H3 Threonine phosphorylation regulates asymmetric histone inheritance in the Drosophila male germline, Cell, 163(4): 920–933. PMCID: PMC4636931.
4. Xie, J.*, Wooten, M.*, Tran, V. and Chen, X. (2017) Breaking symmetry—asymmetry histone inheritance in stem cells. Invited review to Trends in Cell Biology, PMID: 28268050, PMCID: in progress (* equal contribution).