PNP (Purine Nucleoside Phosphorylase)

Gurbanov, Rafig; Tunçer, Sinem

doi:10.4267/2042/68966

Cited by 1 publication

(1 citation statement)

References 20 publications

(34 reference statements)

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“…Both pharmacological and genetic inhibition of MPC1 activates quiescent NSCs by shifting metabolism away from oxidative phosphorylation and toward glycolysis ( 36 ), in alignment with the simulated results. Exploring other predictions in this category shows that several genes are involved in bile acid synthesis, including 3 beta-hydroxysteroid dehydrogenase type 7 (HSD3B7) and cholesterol 7α-hydroxylase (CYP7A1) ( 37 ), and several are involved in nucleotide metabolism such as purine nucleoside phosphorylase (PNP), guanylate kinase 1 (GUK1), and adenosine deaminase (ADA) ( 38–40 ).…”

Section: Resultsmentioning

confidence: 99%

Leveraging metabolic modeling and machine learning to uncover modulators of quiescence depth

Eames,

Chandrasekaran

2023

PNAS Nexus

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Quiescence, a temporary withdrawal from the cell cycle, plays a key role in tissue homeostasis and regeneration. Quiescence is increasingly viewed as a continuum between shallow and deep quiescence, reflecting different potentials to proliferate. The depth of quiescence is altered in a range of diseases and during aging. Here, we leveraged genome-scale metabolic modeling to define the metabolic and epigenetic changes that take place with quiescence deepening. We discovered contrasting changes in lipid catabolism and anabolism, and diverging trends in histone methylation and acetylation. We then built a multi-cell-type machine learning model that accurately predicts quiescence depth in diverse biological contexts. Using both machine-learning and genome-scale flux simulations, we performed high-throughput screening of chemical and genetic modulators of quiescence and identified novel small molecule and genetic modulators with relevance to cancer and aging.

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Section: Resultsmentioning

confidence: 99%