Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation

   November 24th, 2020 at 7:56pm



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 Statement The authors have declared no competing interest.


Giancarlo Bonora  •  Vijay Ramani  •  Ritambhara Singh  •  He Fang  •  Dana Jackson  •  Sanjay Srivatsan  •  Ruolan Qiu  •  Choli Lee  •  Cole Trapnell  •  Jay Shendure  •  Zhijun Duan  •  Xinxian Deng  •  William S. Noble  •  Christine M. Disteche






November 20th, 2020

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