| RRC ID |
72193
|
| Author |
Morimoto Y, Tokumitsu A, Sone T, Hirota Y, Tamura R, Sakamoto A, Nakajima K, Toda M, Kawakami Y, Okano H, Ohta S.
|
| Title |
TPT1 Supports Proliferation of Neural Stem/Progenitor Cells and Brain Tumor Initiating Cells Regulated by Macrophage Migration Inhibitory Factor (MIF).
|
| Journal |
Neurochem Res
|
| Abstract |
One of the key areas in stem cell research is the identification of factors capable of promoting the expansion of Neural Stem Cell/Progenitor Cells (NSPCs) and understanding their molecular mechanisms for future use in clinical settings. We previously identified Macrophage Migration Inhibitory Factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs based on in vitro functional cloning strategy and revealed that MIF can support the proliferation of human brain tumor-initiating cells (BTICs). However, the detailed downstream signaling for the functions has largely remained unknown. Thus, in the present study, we newly identified translationally-controlled tumor protein-1 (TPT1), which is expressed in the ventricular zone of mouse embryonic brain, as a downstream target of MIF signaling in mouse and human NSPCs and human BTICs. Using gene manipulation (over or downregulation of TPT1) techniques including CRISPR/Cas9-mediated heterozygous gene disruption showed that TPT1 contributed to the regulation of cell proliferation/survival in mouse NSPCs, human embryonic stem cell (hESC) derived-NSPCs, human-induced pluripotent stem cells (hiPSCs) derived-NSPCs and BTICs. Furthermore, gene silencing of TPT1 caused defects in neuronal differentiation in the NSPCs in vitro. We also identified the MIF-CHD7-TPT1-SMO signaling axis in regulating hESC-NSPCs and BTICs proliferation. Intriguingly, TPT1suppressed the miR-338 gene, which targets SMO in hESC-NSPCs and BTICs. Finally, mice with implanted BTICs infected with lentivirus-TPT1 shRNA showed a longer overall survival than control. These results also open up new avenues for the development of glioma therapies based on the TPT1 signaling pathway.
|
| Volume |
47(9)
|
| Pages |
2741-2756
|
| Published |
2022-9-1
|
| DOI |
10.1007/s11064-022-03629-6
|
| PII |
10.1007/s11064-022-03629-6
|
| PMID |
35622214
|
| MeSH |
Animals
Brain / metabolism
Cell Proliferation / physiology
Humans
Intramolecular Oxidoreductases
Macrophage Migration-Inhibitory Factors* / genetics
Macrophage Migration-Inhibitory Factors* / metabolism
Mice
MicroRNAs / metabolism
Neoplasm Proteins / metabolism
Neoplastic Stem Cells* / metabolism
Neural Stem Cells* / metabolism
Tumor Protein, Translationally-Controlled 1* / genetics
|
| IF |
3.038
|
| Resource |
| Human and Animal Cells |
201B7(HPS0063) |
