PMID- 38153672 OWN - NLM STAT- MEDLINE DCOM- 20240104 LR - 20240221 IS - 2212-5469 (Electronic) IS - 1738-2696 (Print) IS - 1738-2696 (Linking) VI - 21 IP - 1 DP - 2024 Jan TI - Long and Short-Term Effect of mTOR Regulation on Cerebral Organoid Growth and Differentiations. PG - 159-169 LID - 10.1007/s13770-023-00611-3 [doi] AB - BACKGROUND: The mammalian target of rapamycin (mTOR) signaling is critical for the maintenance and differentiation of neurogenesis, and conceivably for many other brain developmental processes. However, in vivo studies of mTOR functions in the brain are often hampered due to the essential role of the associated signaling in brain development. METHODS: We monitored the long- and short-term effects of mTOR signaling regulation on cerebral organoids growth, differentiation and function using an mTOR inhibitor (everolimus) and an mTOR activator (MHY1485). RESULTS: Short-term treatment with MHY1485 induced faster organoid growth and differentiation, while long-term treatment induced the maturation of cerebral organoids. CONCLUSION: These data suggest that the optimal activity of mTOR is crucial in maintaining normal brain development, and its role is not confined to the early neurogenic phase of brain development. CI - (c) 2023. Korean Tissue Engineering and Regenerative Medicine Society. FAU - Park, Sung Bum AU - Park SB AD - Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. FAU - Lim, Byungho AU - Lim B AD - Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. FAU - Kim, Ki Young AU - Kim KY AD - Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. kykim@krict.re.kr. FAU - Koh, Byumseok AU - Koh B AUID- ORCID: 0000-0002-1106-1891 AD - Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. bkoh@krict.re.kr. LA - eng GR - 2021R1A2C2011195/Ministry of Science and ICT/ GR - 20009774/Ministry of Trade, Industry and Energy/ GR - KK2331-40/Korea Research Institute of Chemical Technology/ PT - Journal Article DEP - 20231228 PL - Korea (South) TA - Tissue Eng Regen Med JT - Tissue engineering and regenerative medicine JID - 101699923 RN - 9HW64Q8G6G (Everolimus) RN - W36ZG6FT64 (Sirolimus) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - *Everolimus MH - Organoids/metabolism MH - Signal Transduction MH - *Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/metabolism MH - Brain/growth & development PMC - PMC10764682 OTO - NOTNLM OT - Cerebral organoids OT - Differentiation OT - Growth OT - mTOR regulation COIS- The authors have no potential conflict of interest. EDAT- 2023/12/28 12:41 MHDA- 2024/01/04 11:43 PMCR- 2024/12/28 CRDT- 2023/12/28 11:26 PHST- 2023/08/03 00:00 [received] PHST- 2023/10/29 00:00 [accepted] PHST- 2023/09/20 00:00 [revised] PHST- 2024/12/28 00:00 [pmc-release] PHST- 2024/01/04 11:43 [medline] PHST- 2023/12/28 12:41 [pubmed] PHST- 2023/12/28 11:26 [entrez] AID - 10.1007/s13770-023-00611-3 [pii] AID - 611 [pii] AID - 10.1007/s13770-023-00611-3 [doi] PST - ppublish SO - Tissue Eng Regen Med. 2024 Jan;21(1):159-169. doi: 10.1007/s13770-023-00611-3. Epub 2023 Dec 28.