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Systems-level identification of key transcription factors in immune cell specification
Transcription factors (TFs) are crucial for regulating cell differentiation during the development of the immune system. However, the key TFs for orchestrating the specification of distinct immune cells are not fully understood. Here, we integrated the transcriptomic and epigenomic measurements in 7...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536753/ https://www.ncbi.nlm.nih.gov/pubmed/36156073 http://dx.doi.org/10.1371/journal.pcbi.1010116 |
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author | Liu, Cong Omilusik, Kyla Toma, Clara Kurd, Nadia S. Chang, John T. Goldrath, Ananda W. Wang, Wei |
author_facet | Liu, Cong Omilusik, Kyla Toma, Clara Kurd, Nadia S. Chang, John T. Goldrath, Ananda W. Wang, Wei |
author_sort | Liu, Cong |
collection | PubMed |
description | Transcription factors (TFs) are crucial for regulating cell differentiation during the development of the immune system. However, the key TFs for orchestrating the specification of distinct immune cells are not fully understood. Here, we integrated the transcriptomic and epigenomic measurements in 73 mouse and 61 human primary cell types, respectively, that span the immune cell differentiation pathways. We constructed the cell-type-specific transcriptional regulatory network and assessed the global importance of TFs based on the Taiji framework, which is a method we have previously developed that can infer the global impact of TFs using integrated transcriptomic and epigenetic data. Integrative analysis across cell types revealed putative driver TFs in cell lineage-specific differentiation in both mouse and human systems. We have also identified TF combinations that play important roles in specific developmental stages. Furthermore, we validated the functions of predicted novel TFs in murine CD8(+) T cell differentiation and showed the importance of Elf1 and Prdm9 in the effector versus memory T cell fate specification and Kdm2b and Tet3 in promoting differentiation of CD8(+) tissue resident memory (Trm) cells, validating the approach. Thus, we have developed a bioinformatic approach that provides a global picture of the regulatory mechanisms that govern cellular differentiation in the immune system and aids the discovery of novel mechanisms in cell fate decisions. |
format | Online Article Text |
id | pubmed-9536753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-95367532022-10-07 Systems-level identification of key transcription factors in immune cell specification Liu, Cong Omilusik, Kyla Toma, Clara Kurd, Nadia S. Chang, John T. Goldrath, Ananda W. Wang, Wei PLoS Comput Biol Research Article Transcription factors (TFs) are crucial for regulating cell differentiation during the development of the immune system. However, the key TFs for orchestrating the specification of distinct immune cells are not fully understood. Here, we integrated the transcriptomic and epigenomic measurements in 73 mouse and 61 human primary cell types, respectively, that span the immune cell differentiation pathways. We constructed the cell-type-specific transcriptional regulatory network and assessed the global importance of TFs based on the Taiji framework, which is a method we have previously developed that can infer the global impact of TFs using integrated transcriptomic and epigenetic data. Integrative analysis across cell types revealed putative driver TFs in cell lineage-specific differentiation in both mouse and human systems. We have also identified TF combinations that play important roles in specific developmental stages. Furthermore, we validated the functions of predicted novel TFs in murine CD8(+) T cell differentiation and showed the importance of Elf1 and Prdm9 in the effector versus memory T cell fate specification and Kdm2b and Tet3 in promoting differentiation of CD8(+) tissue resident memory (Trm) cells, validating the approach. Thus, we have developed a bioinformatic approach that provides a global picture of the regulatory mechanisms that govern cellular differentiation in the immune system and aids the discovery of novel mechanisms in cell fate decisions. Public Library of Science 2022-09-26 /pmc/articles/PMC9536753/ /pubmed/36156073 http://dx.doi.org/10.1371/journal.pcbi.1010116 Text en © 2022 Liu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Liu, Cong Omilusik, Kyla Toma, Clara Kurd, Nadia S. Chang, John T. Goldrath, Ananda W. Wang, Wei Systems-level identification of key transcription factors in immune cell specification |
title | Systems-level identification of key transcription factors in immune cell specification |
title_full | Systems-level identification of key transcription factors in immune cell specification |
title_fullStr | Systems-level identification of key transcription factors in immune cell specification |
title_full_unstemmed | Systems-level identification of key transcription factors in immune cell specification |
title_short | Systems-level identification of key transcription factors in immune cell specification |
title_sort | systems-level identification of key transcription factors in immune cell specification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536753/ https://www.ncbi.nlm.nih.gov/pubmed/36156073 http://dx.doi.org/10.1371/journal.pcbi.1010116 |
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