| Accession |
PRJCA005594 |
| Title |
Single-Cell RNA-seq Analysis of Diabetic Patients Testis Reveals Abnormal Transcriptional Signatures of Sertoli cell and Blood-Testis Barrier Dysfunction |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
Raw sequence reads
|
| Organisms |
Mus musculus
Homo sapiens
|
| Description |
Type 2 diabetes mellitus is one of the most prevalent metabolic diseases affecting multiple organs, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contribute to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we performed smart-seq2 to examine the transcriptome of diabetic patients' testis cells at single cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure were dramatically impaired. Among the deregulated pathways, the Apelin (APLN) peptide /Apelin-receptor (APJ) axis was hyper-activated in diabetic patients. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppressed the production of carnitine and repressed the expression of cell adhesion genes in Sertoli cells. Together, these effects culminated in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorated the BTB damage and, importantly, improved functional spermatogenesis in diabetic db/db micse. We also translated and validated these findings in cultured human testis. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients. |
| Sample scope |
Single cell |
| Release date |
2024-09-25 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 36443325
|
Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models
|
Nature Communications
|
10.1038/s41467-022-34990-3
|
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
|
|
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Research and Development Program of China
|
2019YFA0801800
|
|
|
|
| Submitter |
Xiaoyang
Zhao (zhaoxiaoyang@smu.edu.cn)
|
| Organization |
Southern Medical University |
| Submission date |
2021-06-24 |
