XLin28 enhances tissue repair by reprogramming cellular metabolism

Ng Shyh-Chang; Hao Zhu; T. Yvanka De Soysa; Gen Shinoda; Marc T. Seligson; Kaloyan M. Tsanov; Liem Nguyen; John M. Asara; Lewis C. Cantley; George Q. Daley

doi:10.1016/j.cell.2013.09.059

XLin28 enhances tissue repair by reprogramming cellular metabolism

Ng Shyh-Chang, Hao Zhu, T. Yvanka De Soysa, Gen Shinoda, Marc T. Seligson, Kaloyan M. Tsanov, Liem Nguyen, John M. Asara, Lewis C. Cantley, George Q. Daley

Research output: Contribution to journal › Article › peer-review

286 Scopus citations

Abstract

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

Original language	English (US)
Pages (from-to)	778
Number of pages	1
Journal	Cell
Volume	155
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2013.09.059
State	Published - Nov 7 2013

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2013.09.059

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@article{594e3202cf274f639cd89ba7f39beb63,

title = "XLin28 enhances tissue repair by reprogramming cellular metabolism",

abstract = "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",

author = "Ng Shyh-Chang and Hao Zhu and {Yvanka De Soysa}, T. and Gen Shinoda and Seligson, {Marc T.} and Tsanov, {Kaloyan M.} and Liem Nguyen and Asara, {John M.} and Cantley, {Lewis C.} and Daley, {George Q.}",

note = "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. ",

year = "2013",

month = nov,

day = "7",

doi = "10.1016/j.cell.2013.09.059",

language = "English (US)",

volume = "155",

pages = "778",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

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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

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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 -

XLin28 enhances tissue repair by reprogramming cellular metabolism

Abstract

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