LIN28A Enhances Regenerative Capacity of Human Somatic Tissue Stem Cells Via Metabolic and Mitochondrial Reprogramming

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2021 Sep 24

PMID 34556809

Citations 9

Authors

Kelvin Pieknell

Yanuar Alan Sulistio

Noviana Wulansari

Wahyu Handoko Wibowo Darsono

Mi-Yoon Chang

Ji-Yun Ko

Jong Wook Chang

Min-Jeong Kim

Man Ryul Lee

Sang A Lee

Hyunbeom Lee

Gakyung Lee

Byung Hwa Jung

Hyunbum Park

Geun-Ho Kim

Doory Kim

Gayoung Cho

Chun-Hyung Kim

Dat Da Ly

Kyu-Sang Park

Sang-Hun Lee

Affiliations

Soon will be listed here.

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.

Citing Articles

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Yan L, Sun J, Wang Y, Liu X, Hu J, Sun M BDJ Open. 2024; 10(1):17.

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