期刊
AGING-US
卷 13, 期 3, 页码 4063-4078出版社
IMPACT JOURNALS LLC
关键词
PRPS1/2; pluripotent stem cells; purine biosynthesis; stemness; apoptosis
资金
- National Natural Science Foundation of China [81972341, 81772663, 82072896, 81874078, 81900158, 81703089, 81600078]
- Pudong New Area Science and Technology Development Fund [PKJ2018-Y47]
- Shanghai Jiao Tong University Medical Engineering Cross Fund [YG2017MS32]
- Local High Level University Construction Project of Shanghai Jiao Tong University School of Medicine
- Shanghai Municipal Science and Technology Commission [19JC1413500]
- National Science and Technology Major Project [2018ZX10302206]
The study reveals that the purine synthesis enzymes PRPS1/2 play critical roles in pluripotent stem cell stemness and survival. Knockout of PRPS1 leads to DNA damage and apoptosis in PSCs, while depletion of PRPS2 attenuates stemness and promotes differentiation in PSCs.
Pluripotent stem cells (PSCs) have a unique energetic and biosynthetic metabolism compared with typically differentiated cells. However, the metabolism profiling of PSCs and its underlying mechanism are still unclear. Here, we report PSCs metabolism profiling and identify the purine synthesis enzymes, phosphoribosyl pyrophosphate synthetase 1/2 (PRPS1/2), are critical for PSCs stemness and survival. Ultra-high performance liquid chromatography/mass spectroscopy (UHPLC-MS) analysis revealed that purine synthesis intermediate metabolite levels in PSCs are higher than that in somatic cells. Ectopic expression of PRPS1/2 did not improve purine biosynthesis, drug resistance, or stemness in PSCs. However, knockout of PRPS1 caused PSCs DNA damage and apoptosis. Depletion of PRPS2 attenuated PSCs stemness and assisted PSCs differentiation. Our finding demonstrates that PRPS1/2-mediated purine biosynthesis is critical for pluripotent stem cell stemness and survival.
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