Материал из hpluswiki
Версия от 18:20, 12 мая 2021; OdysseusBot (обсуждение | вклад) (Новая страница: «Cysteine-rich secretory protein LCCL domain-containing 2 precursor (Cysteine-rich secretory protein 11) (CRISP-11) (LCCL domain-containing cysteine-rich secretory...»)
(разн.) ← Предыдущая версия | Текущая версия (разн.) | Следующая версия → (разн.)
Перейти к навигации Перейти к поиску

Cysteine-rich secretory protein LCCL domain-containing 2 precursor (Cysteine-rich secretory protein 11) (CRISP-11) (LCCL domain-containing cysteine-rich secretory protein 2) [CRISP11] [LCRISP2] [UNQ2914/PRO1156/PRO9783]


A large-scale CRISPR screen and identification of essential genes in cellular senescence bypass.

Cellular senescence is an important mechanism of autonomous tumor suppression, while its consequence such as the senescence-associated secretory phenotype (SASP) may drive tumorigenesis and age-related diseases. Therefore, controlling the cell fate optimally when encountering senescence stress is helpful for anti-cancer or anti-aging treatments. To identify genes essential for senescence establishment or maintenance, we carried out a CRISPR-based screen with a deliberately designed single-guide RNA (sgRNA) library. The library comprised of about 12,000 kinds of sgRNAs targeting 1378 senescence-associated genes selected by integrating the information of literature mining, protein-protein interaction network, and differential gene expression. We successfully detected a dozen gene deficiencies potentially causing senescence bypass, and their phenotypes were further validated with a high true positive rate. RNA-seq analysis showed distinct transcriptome patterns of these bypass cells. Interestingly, in the bypass cells, the expression of SASP genes was maintained or elevated with CHEK2, HAS1, or MDK deficiency; but neutralized with MTOR, CRISPLD2, or MORF4L1 deficiency. Pathways of some age-related neurodegenerative disorders were also downregulated with MTOR, CRISPLD2, or MORF4L1 deficiency. The results demonstrated that disturbing these genes could lead to distinct cell fates as a consequence of senescence bypass, suggesting that they may play essential roles in cellular senescence.

MeSH Terms

  • CRISPR-Associated Protein 9
  • CRISPR-Cas Systems
  • Cell Line
  • Cellular Senescence
  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Lentivirus


  • SASP
  • aging
  • bypass
  • cellular senescence