| 项目编号 |
PRJCA005396 |
| 项目标题 |
Single-cell multi-omics sequencing reveals the reprogramming barriers inherent to round spermatid injection embryos |
| 涉及领域 |
Medical |
| 数据类型 |
Whole genome sequencing
Transcriptome or Gene expression
Raw sequence reads
|
| 物种名称 |
Mus musculus
|
| 描述信息 |
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. |
| 样品范围 |
Single cell |
| 发布日期 |
2022-06-28 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 35947654
|
Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection
|
Science Advances
|
10.1126/sciadv.abm3976
|
2022
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| 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
|
|
|
|
| 提交者 |
Xiaoyang
Zhao (zhaoxiaoyang@smu.edu.cn)
|
| 提交单位 |
Southern Medical University |
| 提交日期 |
2021-06-07 |
