Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State

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Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State. / Sinenko, Sergey A.; Kuzmin, Andrey A.; Skvortsova, Elena V.; Ponomartsev, Sergey V.; Efimova, Evgeniya V.; Bader, Michael; Alenina, Natalia; Tomilin, Alexey N.

In: International Journal of Molecular Sciences, Vol. 24, No. 5, 4862, 02.03.2023.

Research output: Contribution to journal › Article › peer-review

Author

Sinenko, Sergey A. ; Kuzmin, Andrey A. ; Skvortsova, Elena V. ; Ponomartsev, Sergey V. ; Efimova, Evgeniya V. ; Bader, Michael ; Alenina, Natalia ; Tomilin, Alexey N. / Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State. In: International Journal of Molecular Sciences. 2023 ; Vol. 24, No. 5.

BibTeX

@article{3a725c7e0f584aeab147b0e6c41a2cea,

title = "Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State",

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 = "Animals, Cellular Reprogramming, Fibroblasts/metabolism, Mice, Pluripotent Stem Cells, Serotonin/biosynthesis, Tryptophan Hydroxylase/metabolism, Tryptophan/metabolism",

author = "Sinenko, {Sergey A.} and Kuzmin, {Andrey A.} and Skvortsova, {Elena V.} and Ponomartsev, {Sergey V.} and Efimova, {Evgeniya V.} and Michael Bader and Natalia Alenina and Tomilin, {Alexey N.}",

year = "2023",

month = mar,

day = "2",

doi = "10.3390/ijms24054862",

language = "English",

volume = "24",

journal = "International Journal of Molecular Sciences",

issn = "1422-0067",

publisher = "MDPI AG",

number = "5",

}

RIS

TY - JOUR

T1 - Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State

AU - Sinenko, Sergey A.

AU - Kuzmin, Andrey A.

AU - Skvortsova, Elena V.

AU - Ponomartsev, Sergey V.

AU - Efimova, Evgeniya V.

AU - Bader, Michael

AU - Alenina, Natalia

AU - Tomilin, Alexey N.

PY - 2023/3/2

Y1 - 2023/3/2

N2 - 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.

AB - 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.

KW - Animals

KW - Cellular Reprogramming

KW - Fibroblasts/metabolism

KW - Mice

KW - Pluripotent Stem Cells

KW - Serotonin/biosynthesis

KW - Tryptophan Hydroxylase/metabolism

KW - Tryptophan/metabolism

UR - https://www.mendeley.com/catalogue/64b8b6b5-e475-3604-8c3f-da6afaf5cc5c/

U2 - 10.3390/ijms24054862

DO - 10.3390/ijms24054862

M3 - Article

C2 - 36902295

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 5

M1 - 4862

ER -

ID: 104540014