Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells

Shan, Hezhen; Geng, Li; Jiang, Xiaoyu; Song, Moshi; Wang, Jianxun; Liu, Zunpeng; Xiao, Zhuo; Wu, Zeming; Hu, Jianli; Ji, Zhejun; Wang, Si; Chan, Piu; Qu, Jing; Zhang, Weiqi; Guang-hui, Liu

doi:10.1007/s13238-021-00872-5

Cited by 23 publications

(14 citation statements)

References 15 publications

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“…1 F and 1 G). Similarly, we did not detect any remarkable differences in the expression of nuclear lamina-associated protein LAP2 and heterochromatin relevant proteins HP1α and H3K9me3, whose downregulation was associated with stem cell senescence (Shan et al, 2021 ; Li et al, 2022 ), between FTO +/+ and FTO −/− hESCs (Figs. 1 H and S1I–K).…”

supporting

confidence: 50%

FTO stabilizes MIS12 and counteracts senescence

Zhang

Shi

et al. 2022

Protein Cell

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supporting

confidence: 50%

FTO stabilizes MIS12 and counteracts senescence

Zhang

Shi

et al. 2022

Protein Cell

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“…S1a-c). In human stem cell model, young wild-type hMSCs manifested higher selfrenewal and regenerative abilities relative to prematurely aged control (WRN-depleted hMSCs, mimicking Werner syndrome (WS), a human progeroid syndrome) [22][23][24][25][26][27] (Fig. 1a and Supplementary Fig.…”

Section: Transcriptomic Analysis Revealing Convergent Metabolic Pathways In Models With Enhanced Regenerative Potentialsmentioning

confidence: 99%

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

Liu

Geng

et al. 2022

Cell Discov

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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.

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“…Through the continuous replenishment of differentiated cells, stem cells support tissue homeostasis and respond to tissue injuries. Given the promising applications of stem cells in cell therapy and regenerative medicine, insights into molecular events underlying stem cell maintenance, self-renewal ability and pluripotency, continue to garner strong interest (Shan et al, 2021 ). Although metabolic pathways have been implicated in the reciprocal regulations of stem cell self-renewal and differentiation as well as organ homeostatic maintenance (Garcia-Prat et al, 2017 ), central aspects of how metabolic requirements differ and are regulated across the various types of human stem cells in our body remain enigmatic.…”

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confidence: 99%