Pieknell, Kelvin Sulistio, Yanuar Alan Wulansari, Noviana Darsono, Wahyu Handoko Wibowo Chang, Mi-Yoon Ko, Ji-Yun Chang, Jong Wook Kim, Min-Jeong Lee, Man Ryul Lee, Sang A. Lee, Hyunbeom Lee, Gakyung Jung, Byung Hwa Park, Hyunbum Kim, Geun-ho Kim, Doory Cho, Gayoung Kim, Chun-Hyung Ly, Dat Da Park, Kyu-Sang Lee, Sang-Hun 2024-01-19T12:33:07Z 2024-01-19T12:33:07Z 2022-01-10 2022-03 1350-9047 https://pubs.kist.re.kr/handle/201004/115622 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. English Nature Publishing Group LIN28A enhances regenerative capacity of human somatic tissue stem cells via metabolic and mitochondrial reprogramming Article 10.1038/s41418-021-00873-1 1 Cell Death and Differentiation, v.29, no.3, pp.540 - 555 Cell Death and Differentiation 29 3 540 555 N scie scopus 000698573500001 2-s2.0-85115401645 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article CYTOCHROME-C RELEASE PROTEIN-KINASE ANTIOXIDANT ENZYMES RESPIRATORY-CHAIN GENE-EXPRESSION GLYCOLYSIS REGULATOR HOMEOSTASIS PROFILE LIN-28