Differential Histone Distribution Patterns in Induced Asymmetrically Dividing Mouse Embryonic Stem Cells
Binbin Ma,
Tung-Jui Trieu,
Ji Cheng,
Shuang Zhou,
Qingsong Tang,
Jing Xie,
Ji-Long Liu,
Keji Zhao,
Shukry J. Habib,
Xin Chen
Affiliations
Binbin Ma
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA; Research Center for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China; Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China
Tung-Jui Trieu
Centre for Stem Cells and Regenerative Medicine, King’s College London, London SE1 9RT, UK
Ji Cheng
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA
Shuang Zhou
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Qingsong Tang
Systems Biology Center, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, USA
Jing Xie
Research Center for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China
Ji-Long Liu
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Keji Zhao
Systems Biology Center, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, USA
Shukry J. Habib
Centre for Stem Cells and Regenerative Medicine, King’s College London, London SE1 9RT, UK
Xin Chen
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA; Corresponding author
Summary: Wnt3a-coated beads can induce asymmetric divisions of mouse embryonic stem cells (mESCs), resulting in one self-renewed mESC and one differentiating epiblast stem cell. This provides an opportunity for studying histone inheritance pattern at a single-cell resolution in cell culture. Here, we report that mESCs with Wnt3a-bead induction display nonoverlapping preexisting (old) versus newly synthesized (new) histone H3 patterns, but mESCs without Wnt3a beads have largely overlapping patterns. Furthermore, H4K20me2/3, an old histone-enriched modification, displays a higher instance of asymmetric distribution on chromatin fibers from Wnt3a-induced mESCs than those from non-induced mESCs. These locally distinct distributions between old and new histones have both cellular specificity in Wnt3a-induced mESCs and molecular specificity for histones H3 and H4. Given that post-translational modifications at H3 and H4 carry the major histone modifications, our findings provide a mammalian cell culture system to study histone inheritance for maintaining stem cell fate and for resetting it during differentiation.
