RT Journal Article
SR Electronic
T1 Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.20.390765
DO 10.1101/2020.11.20.390765
A1 Giancarlo Bonora
A1 Vijay Ramani
A1 Ritambhara Singh
A1 He Fang
A1 Dana Jackson
A1 Sanjay Srivatsan
A1 Ruolan Qiu
A1 Choli Lee
A1 Cole Trapnell
A1 Jay Shendure
A1 Zhijun Duan
A1 Xinxian Deng
A1 William S. Noble
A1 Christine M. Disteche
YR 2020
UL http://biorxiv.org/content/early/2020/11/20/2020.11.20.390765.abstract
AB 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.