| Title: |
Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State. |
| Authors: |
Sinenko, Sergey A.; Kuzmin, Andrey A.; Skvortsova, Elena V.; Ponomartsev, Sergey V.; Efimova, Evgeniya V.; Bader, Michael; Alenina, Natalia; Tomilin, Alexey N. |
| Source: |
International Journal of Molecular Sciences; Mar2023, Vol. 24 Issue 5, p4862, 14p |
| Subject Terms: |
Serotonin receptors; Induced pluripotent stem cells; Serotonin; Biosynthesis; Tryptophan; Mammal development |
| 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. [ABSTRACT FROM AUTHOR] |
| : |
Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |