Inhibition of neural stem cell aging through the transient induction of reprogramming factors.
Min Ji HanWon Ji LeeJoonhyuk ChoiYean Ju HongSang Jun UhmYoungsok ChoiJeong-Tae DoPublished in: The Journal of comparative neurology (2020)
Adult stem cells age during long-term in vitro culture, and neural stem cells (NSCs), which can self-renew and differentiate into neurons and glial cells, also display reduced differentiation potential after repeated passaging. However, the mechanistic details underlying this process remain unclear. In this study, we found that long-term in vitro culture of NSCs resulted in aging-related upregulation of inflammatory- and endoplasmic reticulum (ER) stress-related genes, including the proinflammatory cytokines interleukin (IL)1β and IL6, the senescence-associated enzyme matrix metallopeptidase 13 (MMP13), and the ER stress-responsive transcription factor activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). However, the cyclic and transient induction of four reprogramming factors (POU domain, class 5, transcription factor 1, also known as octamer-binding transcription factor 4; SRY [sex determining region Y]-box 2; Kruppel-like factor 4; and myelocytomatosis oncogene; collectively referred to as OSKM) can inhibit NSC aging, as indicated by the decreased expression of the inflammatory and ER stress-related genes. We used ROSA-4F NSCs, which express OSKM from only one allele, to minimize the potential for full reprogramming or tumor formation during NSC rejuvenation. We expect that this novel rejuvenation method will enhance the potential of NSCs as a clinical approach to the treatment of neurological diseases.
Keyphrases
- transcription factor
- stem cells
- dna binding
- endoplasmic reticulum
- poor prognosis
- neural stem cells
- binding protein
- induced apoptosis
- dna damage
- oxidative stress
- genome wide identification
- human health
- signaling pathway
- cerebral ischemia
- diffuse large b cell lymphoma
- endoplasmic reticulum stress
- risk assessment
- neuropathic pain
- drug delivery
- mesenchymal stem cells
- endothelial cells
- spinal cord injury
- dna repair
- bone marrow
- brain injury
- platelet rich plasma
- subarachnoid hemorrhage
- cell death