Procr-KO Mouse

Procr, short for Protein C Receptor, functions as a signaling receptor. It is involved in the maintenance and self-renewal of various stem and progenitor cells. It interacts with ligand protein C, recruiting HSP90AA1, Src, and IGF1R, and is thus essential for the regulation of mammary stem cells through this signaling complex [3].

In adult mouse pancreas, Procr+ cells are a previously unidentified population. Genetic lineage tracing shows they can clonally expand and generate all four endocrine cell types during adult homeostasis. Sorted Procr+ cells can form islet-like organoids, which can be expanded long-term and differentiated into insulin-secreting, glucose-responsive β-dominant organoids that reverse diabetes in mice upon transplantation [1,4]. In the ovarian surface epithelium (OSE), Procr marks progenitor cells responsible for OSE repair post-ovulation. Targeted ablation of Procr+ cells impedes the repair process, and selective YAP activation in Procr cells is essential for OSE stem/progenitor expansion and repair [5,6]. Also, in heterotopic ossification, calcified apoptotic vesicles from PROCR+ fibroblasts initiate the abnormal formation of ectopic bone [2].

In conclusion, Procr is crucial for the maintenance and function of stem and progenitor cells in multiple tissues. Studies using gene-targeted mouse models, such as KO or CKO in mammary stem cells, pancreatic islet progenitors, and OSE cells, have revealed its role in tissue development, homeostasis, and disease-related processes like diabetes and heterotopic ossification. These models have provided valuable insights into the biological functions of Procr, highlighting its potential as a therapeutic target in relevant diseases.

References:

1. Wang, Daisong, Wang, Jingqiang, Bai, Lanyue, Clevers, Hans, Zeng, Yi Arial. . Long-Term Expansion of Pancreatic Islet Organoids from Resident Procr+ Progenitors. In Cell, 180, 1198-1211.e19. doi:10.1016/j.cell.2020.02.048. https://pubmed.ncbi.nlm.nih.gov/32200801/

2. Yan, Jianfei, Gao, Bo, Wang, Chenyu, Zou, Weiguo, Jiao, Kai. . Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification. In Journal of extracellular vesicles, 13, e12425. doi:10.1002/jev2.12425. https://pubmed.ncbi.nlm.nih.gov/38594791/

3. Liu, Chunye, Lin, Changdong, Wang, Daisong, Chen, Jianfeng, Zeng, Yi Arial. . Procr functions as a signaling receptor and is essential for the maintenance and self-renewal of mammary stem cells. In Cell reports, 38, 110548. doi:10.1016/j.celrep.2022.110548. https://pubmed.ncbi.nlm.nih.gov/35320720/

4. Wang, Jingqiang, Wang, Daisong, Chen, Xinyi, Liu, Chunye, Zeng, Yi Arial. 2022. Isolation of mouse pancreatic islet Procr+ progenitors and long-term expansion of islet organoids in vitro. In Nature protocols, 17, 1359-1384. doi:10.1038/s41596-022-00683-w. https://pubmed.ncbi.nlm.nih.gov/35396545/

5. Wang, Jingqiang, Wang, Daisong, Chu, Kun, Li, Wen, Zeng, Yi Arial. 2019. Procr-expressing progenitor cells are responsible for murine ovulatory rupture repair of ovarian surface epithelium. In Nature communications, 10, 4966. doi:10.1038/s41467-019-12935-7. https://pubmed.ncbi.nlm.nih.gov/31672973/

6. Wang, Jingqiang, Liu, Chunye, He, Lingli, Zhang, Lei, Zeng, Yi Arial. 2022. Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair. In eLife, 11, . doi:10.7554/eLife.75449. https://pubmed.ncbi.nlm.nih.gov/35285801/