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GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program
Cell type-specific transcription factors control stem and progenitor cell transitions by establishing networks containing hundreds of genes and proteins. Network complexity renders it challenging to discover essential versus modulatory or redundant components. This scenario is exemplified by GATA2 r...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905696/ https://www.ncbi.nlm.nih.gov/pubmed/35008108 http://dx.doi.org/10.1182/bloodadvances.2021006182 |
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author | Johnson, Kirby D. Soukup, Alexandra A. Bresnick, Emery H. |
author_facet | Johnson, Kirby D. Soukup, Alexandra A. Bresnick, Emery H. |
author_sort | Johnson, Kirby D. |
collection | PubMed |
description | Cell type-specific transcription factors control stem and progenitor cell transitions by establishing networks containing hundreds of genes and proteins. Network complexity renders it challenging to discover essential versus modulatory or redundant components. This scenario is exemplified by GATA2 regulation of hematopoiesis during embryogenesis. Loss of a far upstream Gata2 enhancer (−77) disrupts the GATA2-dependent transcriptome governing hematopoietic progenitor cell differentiation. The aberrant transcriptome includes the transcription factor interferon regulatory factor 8 (IRF8) and a host of innate immune regulators. Mutant progenitors lose the capacity to balance production of diverse hematopoietic progeny. To elucidate mechanisms, we asked if IRF8 is essential, contributory, or not required. Reducing Irf8, in the context of the −77 mutant allele, reversed granulocytic deficiencies and the excessive accumulation of dendritic cell committed progenitors. Despite many dysregulated components that control vital transcriptional, signaling, and immune processes, the aberrant elevation of a single transcription factor deconstructed the differentiation program. |
format | Online Article Text |
id | pubmed-8905696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-89056962022-03-09 GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program Johnson, Kirby D. Soukup, Alexandra A. Bresnick, Emery H. Blood Adv Hematopoiesis and Stem Cells Cell type-specific transcription factors control stem and progenitor cell transitions by establishing networks containing hundreds of genes and proteins. Network complexity renders it challenging to discover essential versus modulatory or redundant components. This scenario is exemplified by GATA2 regulation of hematopoiesis during embryogenesis. Loss of a far upstream Gata2 enhancer (−77) disrupts the GATA2-dependent transcriptome governing hematopoietic progenitor cell differentiation. The aberrant transcriptome includes the transcription factor interferon regulatory factor 8 (IRF8) and a host of innate immune regulators. Mutant progenitors lose the capacity to balance production of diverse hematopoietic progeny. To elucidate mechanisms, we asked if IRF8 is essential, contributory, or not required. Reducing Irf8, in the context of the −77 mutant allele, reversed granulocytic deficiencies and the excessive accumulation of dendritic cell committed progenitors. Despite many dysregulated components that control vital transcriptional, signaling, and immune processes, the aberrant elevation of a single transcription factor deconstructed the differentiation program. American Society of Hematology 2022-03-02 /pmc/articles/PMC8905696/ /pubmed/35008108 http://dx.doi.org/10.1182/bloodadvances.2021006182 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Hematopoiesis and Stem Cells Johnson, Kirby D. Soukup, Alexandra A. Bresnick, Emery H. GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
title | GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
title_full | GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
title_fullStr | GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
title_full_unstemmed | GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
title_short | GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
title_sort | gata2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program |
topic | Hematopoiesis and Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905696/ https://www.ncbi.nlm.nih.gov/pubmed/35008108 http://dx.doi.org/10.1182/bloodadvances.2021006182 |
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