Accession PRJCA005396
Title Single-cell multi-omics sequencing reveals the reprogramming barriers inherent to round spermatid injection embryos
Relevance Medical
Data types Whole genome sequencing
Transcriptome or Gene expression
Raw sequence reads
Organisms Mus musculus
Description Round spermatid injection (ROSI) technique holds great promise for clinical treatment of infertile men who were diagnosed as that round spermatids are the most mature germ cells. However, the mechanisms underlying the poor developmental potential of both human and mouse ROSI embryos and how to overcome it remains largely unknown. Here, we establish the gene expression, chromatin accessibility and DNA methylation landscapes of mouse ROSI embryos using a single-cell multi-omics approach. Comparative analysis reveals the molecular reprogramming barriers marked by these three layer profiling abnormalities in ROSI embryos despite successful reprogramming globally. Remarkably, we screen out a novel small compound-A366 that can increase the rate of ROSI embryos to blastocyst stage and healthy pub by about 2 times. Finally, we demonstrate that A366 exerts its roles by partial overcoming of the reprogramming barriers; especially, the treatment of A366 could recover the expression of key genes critical for skeleton and chromatin organization, and the re-distribution of γ-tubulin and morphology of male pronucleus. Collectively, our study unveils the molecular reprogramming barriers inherent to ROSI embryos, and identifies A366 to be a potential small molecule to partially overcome these barriers.
Sample scope Single cell
Release date 2022-06-28
Publication
PubMed ID Article title Journal name DOI Year
35947654 Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection Science Advances 10.1126/sciadv.abm3976 2022
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) Key Program 2016YFC1000606
National Natural Science Foundation of China (NSFC) 82071711
National Natural Science Foundation of China (NSFC) 31671544
Key Research & Development Program of Bioland Laboratory 2018GZR110104002
Guangzhou science and technology project key project topic 201904020031
Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory 2018GZR0201003
Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory 2018GZR110102004
National Natural Science Foundation of China (NSFC) 2021YFA1102700
National Natural Science Foundation of China (NSFC) 2020YFA0113200
Submitter Xiaoyang Zhao (zhaoxiaoyang@smu.edu.cn)
Organization Southern Medical University
Submission date 2021-06-07

Project Data

Resource name Description
BioSample (481)  show -
GSA (1) -
CRA004360 Single-cell multi-omics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection