Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor

被引：97

作者：

Liu, Zunpeng ^{[1
,2
,3
]}

Li, Wei ^{[4
,5
]}

Geng, Lingling ^{[4
,5
]}

Sun, Liang ^{[6
,7
]}

Wang, Qiaoran ^{[3
,8
,9
]}

Yu, Yang ^{[10
,11
]}

Yan, Pengze ^{[3
,12
]}

Liang, Chuqian ^{[3
,12
]}

Ren, Jie ^{[2
,3
,8
,9
]}

Song, Moshi ^{[2
,3
,12
]}

Zhao, Qian ^{[4
,5
]}

Lei, Jinghui ^{[4
,5
]}

Cai, Yusheng ^{[2
,12
,13
]}

Li, Jiaming ^{[3
,8
,9
]}

Yan, Kaowen ^{[2
,12
,13
]}

Wu, Zeming ^{[2
,12
,13
]}

Chu, Qun ^{[1
,2
,13
]}

Li, Jingyi ^{[2
,12
,13
]}

Wang, Si ^{[4
,5
]}

Li, Chunyi ^{[14
]}

Han, Jing-Dong J. ^{[15
]}

Hernandez-Benitez, Reyna ^{[16
]}

Shyh-Chang, Ng ^{[1
,2
,3
]}

Belmonte, Juan Carlos Izpisua ^{[16
]}

Zhang, Weiqi ^{[2
,3
,8
,9
]}

Qu, Jing ^{[1
,2
,3
,13
]}

Liu, Guang-Hui ^{[2
,3
,4
,5
,12
,13
]}

机构：

[1] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China

[2] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China

[3] Univ Chinese Acad Sci, Beijing, Peoples R China

[4] Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp, Beijing, Peoples R China

[5] Capital Med Univ, Xuanwu Hosp, Aging Translat Med Ctr, Beijing, Peoples R China

[6] Chinese Acad Med Sci, Inst Geriatr Med, Beijing Inst Geriatr,Key Lab Geriatr, Beijing Hosp,Natl Ctr Gerontol,Natl Hlth Commiss, Beijing, Peoples R China

[7] Kunming Med Univ, NHC Key Lab Drug Addict Med, Kunming, Yunnan, Peoples R China

[8] Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing, Peoples R China

[9] China Natl Ctr Bioinformat, Beijing, Peoples R China

[10] Peking Univ Third Hosp, Ctr Reprod Med, Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing, Peoples R China

[11] Peking Univ Third Hosp, Ctr Reprod Med, Key Lab Assisted Reprod, Dept Obstet & Gynecol,Minist Educ, Beijing, Peoples R China

[12] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China

[13] Beijing Inst Stem Cell & Regenerat Med, Beijing, Peoples R China

[14] Changchun Sci Tech Univ, Inst Antler Sci & Prod Technol, Changchun, Jilin, Peoples R China

[15] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Ctr Quantitat Biol CQB, Beijing, Peoples R China

[16] Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

来源：

CELL DISCOVERY | 2022年 / 8卷 / 01期

基金：

中国国家自然科学基金; 北京市自然科学基金; 国家重点研发计划;

关键词：

GLUTATHIONE METABOLISM; LIMB REGENERATION; DEER ANTLER; MODEL; POLYAMINES; MOLECULES; AXOLOTL; STRESS; GROWTH; CELLS;

D O I：

10.1038/s41421-021-00361-3

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Regenerative capacity declines throughout evolution and with age. In this study, we asked whether metabolic programs underlying regenerative capability might be conserved across species, and if so, whether such metabolic drivers might be harnessed to promote tissue repair. To this end, we conducted metabolomic analyses in two vertebrate organ regeneration models: the axolotl limb blastema and antler stem cells. To further reveal why young individuals have higher regenerative capacity than the elderly, we also constructed metabolic profiles for primate juvenile and aged tissues, as well as young and aged human stem cells. In joint analyses, we uncovered that active pyrimidine metabolism and fatty acid metabolism correlated with higher regenerative capacity. Furthermore, we identified a set of regeneration-related metabolite effectors conserved across species. One such metabolite is uridine, a pyrimidine nucleoside, which can rejuvenate aged human stem cells and promote regeneration of various tissues in vivo. These observations will open new avenues for metabolic intervention in tissue repair and regeneration.

引用

页数：22

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