LIN28A enhances regenerative capacity of human somatic tissue stem cells via metabolic and mitochondrial reprogramming

Title
LIN28A enhances regenerative capacity of human somatic tissue stem cells via metabolic and mitochondrial reprogramming
Authors
정병화이현범이가경Kelvin PieknellYanuar Alan SulistioNoviana WulansariWahyu Handoko Wibowo DarsonoMi-Yoon ChangJi-Yun KoJong Wook ChangMin-Jeong KimMan Ryul LeeSang A. LeeHyunbum ParkGeun-ho KimDoory KimGayoung ChoChun-Hyung KimDat Da LyKyu-Sang ParkSang-Hun Lee
Issue Date
2021-09
Publisher
Cell death and differentiation
Citation
VOL 온라인게재, 온라인게재
Abstract
Developing methods to improve the regenerative capacity of somatic stem cells (SSCs) is a major challenge in regenerative medicine. Here, we propose the forced expression of LIN28A as a method to modulate cellular metabolism, which in turn enhances self-renewal, differentiation capacities, and engraftment after transplantation of various human SSCs. Mechanistically, in undifferentiated/proliferating SSCs, LIN28A induced metabolic reprogramming from oxidative phosphorylation (OxPhos) to glycolysis by activating PDK1-mediated glycolysis-TCA/OxPhos uncoupling. Mitochondria were also reprogrammed into healthy/fused mitochondria with improved functional capacity. The reprogramming allows SSCs to undergo cell proliferation more extensively with low levels of oxidative and mitochondrial stress. When the PDK1-mediated uncoupling was untethered upon differentiation, LIN28A-SSCs differentiated more efficiently with an increase of OxPhos by utilizing the reprogrammed mitochondria. This study provides mechanistic and practical approaches of utilizing LIN28A and metabolic reprogramming in order to improve SSCs utility in regenerative medicine.
URI
https://pubs.kist.re.kr/handle/201004/74062
ISSN
1350-9047
Appears in Collections:
KIST Publication > Article
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