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PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages
Tissue-resident macrophages play a crucial role in maintaining homeostasis. Macrophage progenitors migrate to tissues perinatally, where environmental cues shape their identity and unique functions. Here, we show that the absence of PPARγ affects neonatal development and VCAM-1 expression of splenic...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006858/ https://www.ncbi.nlm.nih.gov/pubmed/33765133 http://dx.doi.org/10.1084/jem.20191314 |
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author | Okreglicka, Katarzyna Iten, Irina Pohlmeier, Lea Onder, Lucas Feng, Qian Kurrer, Michael Ludewig, Burkhard Nielsen, Peter Schneider, Christoph Kopf, Manfred |
author_facet | Okreglicka, Katarzyna Iten, Irina Pohlmeier, Lea Onder, Lucas Feng, Qian Kurrer, Michael Ludewig, Burkhard Nielsen, Peter Schneider, Christoph Kopf, Manfred |
author_sort | Okreglicka, Katarzyna |
collection | PubMed |
description | Tissue-resident macrophages play a crucial role in maintaining homeostasis. Macrophage progenitors migrate to tissues perinatally, where environmental cues shape their identity and unique functions. Here, we show that the absence of PPARγ affects neonatal development and VCAM-1 expression of splenic iron-recycling red pulp macrophages (RPMs) and bone marrow erythroblastic island macrophages (EIMs). Transcriptome analysis of the few remaining Pparg-deficient RPM-like and EIM-like cells suggests that PPARγ is required for RPM and EIM identity, cell cycling, migration, and localization, but not function in mature RPMs. Notably, Spi-C, another transcription factor implicated in RPM development, was not essential for neonatal expansion of RPMs, even though the transcriptome of Spic-deficient RPMs was strongly affected and indicated a loss of identity. Similarities shared by Pparg- and Spic-deficient RPM-like cells allowed us to identify pathways that rely on both factors. PPARγ and Spi-C collaborate in inducing transcriptional changes, including VCAM-1 and integrin α(D )expression, which could be required for progenitor retention in the tissue, allowing access to niche-related signals that finalize differentiation. |
format | Online Article Text |
id | pubmed-8006858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80068582021-11-03 PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages Okreglicka, Katarzyna Iten, Irina Pohlmeier, Lea Onder, Lucas Feng, Qian Kurrer, Michael Ludewig, Burkhard Nielsen, Peter Schneider, Christoph Kopf, Manfred J Exp Med Article Tissue-resident macrophages play a crucial role in maintaining homeostasis. Macrophage progenitors migrate to tissues perinatally, where environmental cues shape their identity and unique functions. Here, we show that the absence of PPARγ affects neonatal development and VCAM-1 expression of splenic iron-recycling red pulp macrophages (RPMs) and bone marrow erythroblastic island macrophages (EIMs). Transcriptome analysis of the few remaining Pparg-deficient RPM-like and EIM-like cells suggests that PPARγ is required for RPM and EIM identity, cell cycling, migration, and localization, but not function in mature RPMs. Notably, Spi-C, another transcription factor implicated in RPM development, was not essential for neonatal expansion of RPMs, even though the transcriptome of Spic-deficient RPMs was strongly affected and indicated a loss of identity. Similarities shared by Pparg- and Spic-deficient RPM-like cells allowed us to identify pathways that rely on both factors. PPARγ and Spi-C collaborate in inducing transcriptional changes, including VCAM-1 and integrin α(D )expression, which could be required for progenitor retention in the tissue, allowing access to niche-related signals that finalize differentiation. Rockefeller University Press 2021-03-25 /pmc/articles/PMC8006858/ /pubmed/33765133 http://dx.doi.org/10.1084/jem.20191314 Text en © 2021 Okreglicka et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Okreglicka, Katarzyna Iten, Irina Pohlmeier, Lea Onder, Lucas Feng, Qian Kurrer, Michael Ludewig, Burkhard Nielsen, Peter Schneider, Christoph Kopf, Manfred PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
title | PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
title_full | PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
title_fullStr | PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
title_full_unstemmed | PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
title_short | PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
title_sort | pparγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006858/ https://www.ncbi.nlm.nih.gov/pubmed/33765133 http://dx.doi.org/10.1084/jem.20191314 |
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