TY - JOUR
T1 - XLin28 enhances tissue repair by reprogramming cellular metabolism
AU - Shyh-Chang, Ng
AU - Zhu, Hao
AU - Yvanka De Soysa, T.
AU - Shinoda, Gen
AU - Seligson, Marc T.
AU - Tsanov, Kaloyan M.
AU - Nguyen, Liem
AU - Asara, John M.
AU - Cantley, Lewis C.
AU - Daley, George Q.
N1 - Funding Information:
We thank John Powers, Costas Lyssiotis, Charles Kaufman, Jessica Lehoczky, and Clifford Tabin for invaluable feedback and discussions; Jin Zhang and the lab of Marcia Haigis for help with the Seahorse Analyzer; Min Yuan and Susanne Breitkopf for help with metabolomics; Samar Shah and Akiko Yabuuchi for help with the mouse work; Asher Bomer for help with the scratch assays; James Thornton for help with northern blots; and Roderick Bronson and the Harvard Medical School Rodent Histopathology Core for mouse tissue pathology. This work was supported by an A ∗ STAR National Science Scholarship to N.S.-C., a Graduate Training in Cancer Research Grant, an American Cancer Society Postdoctoral Fellowship, an NIH K08 grant, and a CPRIT award to H.Z.; a Herchel Smith Graduate Fellowship to K.M.T.; and a grant from the Ellison Medical Foundation to G.Q.D. G.Q.D. is an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research.
PY - 2013/11/7
Y1 - 2013/11/7
N2 - Summary Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly conserved RNA-binding protein expressed during embryogenesis, plays roles in development, pluripotency, and metabolism. To determine whether Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles and accelerated regrowth of cartilage, bone, and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however, let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PaperClip
AB - Summary Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly conserved RNA-binding protein expressed during embryogenesis, plays roles in development, pluripotency, and metabolism. To determine whether Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles and accelerated regrowth of cartilage, bone, and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however, let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PaperClip
UR - http://www.scopus.com/inward/record.url?scp=84887984423&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2013.09.059
DO - 10.1016/j.cell.2013.09.059
M3 - Article
C2 - 24209617
AN - SCOPUS:84887984423
SN - 0092-8674
VL - 155
SP - 778
JO - Cell
JF - Cell
IS - 4
ER -