Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans
T helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammat...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Online Access: | https://hdl.handle.net/10356/80635 http://hdl.handle.net/10220/46573 |
| _version_ | 1826122541378306048 |
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| author | Acerbi, Enzo Viganò, Elena Poidinger, Michael Mortellaro, Alessandra Zelante, Teresa Stella, Fabio |
| author2 | Singapore Centre for Environmental Life Sciences Engineering |
| author_facet | Singapore Centre for Environmental Life Sciences Engineering Acerbi, Enzo Viganò, Elena Poidinger, Michael Mortellaro, Alessandra Zelante, Teresa Stella, Fabio |
| author_sort | Acerbi, Enzo |
| collection | NTU |
| description | T helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammatory conditions. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling TH17 differentiation. From the network, we identified the Prdm1 gene encoding the B lymphocyte-induced maturation protein 1 as a crucial negative regulator of human TH17 cell differentiation. The results have been validated by perturbing Prdm1 expression on freshly isolated CD4+ naïve T cells: reduction of Prdm1 expression leads to augmentation of IL-17 release. These data unravel a possible novel target to control TH17 polarization in inflammatory disorders. Furthermore, this study represents the first in vitro validation of continuous time Bayesian networks as gene network reconstruction method and as hypothesis generation tool for wet-lab biological experiments. |
| first_indexed | 2024-10-01T05:50:10Z |
| format | Journal Article |
| id | ntu-10356/80635 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:50:10Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/806352022-02-16T16:26:43Z Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans Acerbi, Enzo Viganò, Elena Poidinger, Michael Mortellaro, Alessandra Zelante, Teresa Stella, Fabio Singapore Centre for Environmental Life Sciences Engineering PRDM1 Protein, Human Cell Differentiation DRNTU::Science::Biological sciences T helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammatory conditions. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling TH17 differentiation. From the network, we identified the Prdm1 gene encoding the B lymphocyte-induced maturation protein 1 as a crucial negative regulator of human TH17 cell differentiation. The results have been validated by perturbing Prdm1 expression on freshly isolated CD4+ naïve T cells: reduction of Prdm1 expression leads to augmentation of IL-17 release. These data unravel a possible novel target to control TH17 polarization in inflammatory disorders. Furthermore, this study represents the first in vitro validation of continuous time Bayesian networks as gene network reconstruction method and as hypothesis generation tool for wet-lab biological experiments. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2018-11-07T07:41:37Z 2019-12-06T13:53:37Z 2018-11-07T07:41:37Z 2019-12-06T13:53:37Z 2016 Journal Article Acerbi, E., Viganò, E., Poidinger, M., Mortellaro, A., Zelante, T., & Stella, F. (2016). Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans. Scientific Reports, 6, 23128-. doi:10.1038/srep23128 https://hdl.handle.net/10356/80635 http://hdl.handle.net/10220/46573 10.1038/srep23128 26976045 en Scientific Reports © 2016 The Authors (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 7 p. application/pdf |
| spellingShingle | PRDM1 Protein, Human Cell Differentiation DRNTU::Science::Biological sciences Acerbi, Enzo Viganò, Elena Poidinger, Michael Mortellaro, Alessandra Zelante, Teresa Stella, Fabio Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans |
| title | Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans |
| title_full | Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans |
| title_fullStr | Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans |
| title_full_unstemmed | Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans |
| title_short | Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans |
| title_sort | continuous time bayesian networks identify prdm1 as a negative regulator of th17 cell differentiation in humans |
| topic | PRDM1 Protein, Human Cell Differentiation DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/80635 http://hdl.handle.net/10220/46573 |
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