TY - JOUR T1 - Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation JF - bioRxiv DO - 10.1101/2020.11.20.390765 SP - 2020.11.20.390765 AU - Giancarlo Bonora AU - Vijay Ramani AU - Ritambhara Singh AU - He Fang AU - Dana Jackson AU - Sanjay Srivatsan AU - Ruolan Qiu AU - Choli Lee AU - Cole Trapnell AU - Jay Shendure AU - Zhijun Duan AU - Xinxian Deng AU - William S. Noble AU - Christine M. Disteche Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/20/2020.11.20.390765.abstract N2 - Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C. In differentiated cells, contact decay profiles, which clearly distinguish the active and inactive X chromosomes, reveal loss of the inactive X-specific structure at mitosis followed by a rapid reappearance, suggesting a ‘bookkeeping’ mechanism. In differentiating embryonic stem cells, changes in contact decay profiles are detected in parallel on both the X chromosomes and autosomes, suggesting profound simultaneous reorganization. The onset of the inactive X-specific structure in single cells is notably delayed relative to that of gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Novel computational approaches to effectively align single-cell gene expression, chromatin accessibility, and 3D chromosome structure reveal that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility.Competing Interest StatementThe authors have declared no competing interest. ER -