e.g., PRJCA000229; PRJNA784038; human
Accession PRJCA018297
Title Genomic locus of Gm26793 forms an inter-chromosomal molecular lock with Cubn to ensure proper stem cell differentiation and mouse embryogenesis
Relevance Model organism
Data types Epigenomics
Targeted Locus (Loci)
Transcriptome or Gene expression
Single cell sequencing
Organisms Mus musculus
Description 3D genome organization in the mammalian nucleus is modulated by frequent physical interactions between different genomic loci and related factors. These physical chromatin associations, intra-chromosomally or inter-chromosomally, could directly regulate multiple biological processes. However, compared with intra-chromosomal interactions, whether inter-chromosomal interactions are of biological significance in cell lineage establishment remains largely unexplored. Here, we revealed genomic deletion of lncRNA-Gm26793 could preferentially induce the cell fate decision towards primitive endoderm (PrE) lineage of mouse embryonic stem cells (mESCs). Moreover, single-cell RNA sequencing (scRNA-seq) of Gm26793 knockout blastocysts showed nearly 20% cells of arrested embryos resided in epiblast (EPI) state and the expression of Cubn is abnormally activated during the lineage segregation between EPI and PrE. Mechanistically, we found Gm26793 genomic locus acts as a chromatin interaction hub by forming inter-chromosomal contact with Cubn locus. Genomic disruption of the inter-chromosomal anchor upregulated Cubn expression, thus enhancing the PrE differentiation potency of mESCs. Overall, this study provides a paradigm that inter-chromosomal interaction coordinates transcriptional control in the developmental process, which broadens the current understanding of gene regulation in cell lineage specification.
Sample scope Synthetic
Release date 2023-09-09
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) 31630043
Chinese Academy of Sciences (CAS) XDA16020501
Chinese Academy of Sciences (CAS) XDA16020404
National Natural Science Foundation of China (NSFC) 31900573
Submitter liu zhi wen (liuzhiwen2015@sibcb.ac.cn)
Organization Guangzhou Laboratory
Submission date 2023-07-12

Project Data

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