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Tryptophan hydroxylase-2-mediated serotonin biosynthesis suppresses cell reprogramming into pluripotent state

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Item Type:Article
Title:Tryptophan hydroxylase-2-mediated serotonin biosynthesis suppresses cell reprogramming into pluripotent state
Creators Name:Sinenko, S.A., Kuzmin, A.A., Skvortsova, E.V., Ponomartsev, S.V., Efimova, E.V., Bader, M., Alenina, N. and Tomilin, A.N.
Abstract:The monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has important functions both in the neural system and during embryonic development in mammals. In this study, we set out to investigate whether and how endogenous serotonin affects reprogramming to pluripotency. As serotonin is synthesized from tryptophan by the rate limiting enzymes tryptophan hydroxylase-1 and -2 (TPH1 and TPH2), we have assessed the reprogramming of TPH1- and/or TPH2-deficient mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs). The reprogramming of the double mutant MEFs showed a dramatic increase in the efficiency of iPSC generation. In contrast, ectopic expression of TPH2 alone or in conjunction with TPH1 reverted the rate of reprogramming of the double mutant MEFs to the wild-type level and besides, TPH2 overexpression significantly suppressed reprogramming of wild-type MEFs. Our data thus suggest a negative role of serotonin biosynthesis in the reprogramming of somatic cells to a pluripotent state.
Keywords:Serotonin, 5-HT, Pluripotency, Reprogramming, Induced Pluripotent Stem Cells (iPSCs), Tryptophan Hydroxylase 1 and 2 (TPH1 and TPH2), Animals, Mice
Source:International Journal of Molecular Sciences
ISSN:1422-0067
Publisher:MDPI
Volume:24
Number:5
Page Range:4862
Date:2 March 2023
Official Publication:https://doi.org/10.3390/ijms24054862
PubMed:View item in PubMed

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