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Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12

Olfaction depends on lifelong production of sensory neurons from CXCR4 expressing neurogenic stem cells. Signaling by CXCR4 depends on the concentration of CXCL12, CXCR4’s principal ligand. Here, we use several genetic models to investigate how regulation of CXCL12 in the olfactory stem cell niche a...

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Detalles Bibliográficos
Autores principales: Dietz, André, Senf, Katja, Karius, Julia, Stumm, Ralf, Neuhaus, Eva Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486585/
https://www.ncbi.nlm.nih.gov/pubmed/37681896
http://dx.doi.org/10.3390/cells12172164
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author Dietz, André
Senf, Katja
Karius, Julia
Stumm, Ralf
Neuhaus, Eva Maria
author_facet Dietz, André
Senf, Katja
Karius, Julia
Stumm, Ralf
Neuhaus, Eva Maria
author_sort Dietz, André
collection PubMed
description Olfaction depends on lifelong production of sensory neurons from CXCR4 expressing neurogenic stem cells. Signaling by CXCR4 depends on the concentration of CXCL12, CXCR4’s principal ligand. Here, we use several genetic models to investigate how regulation of CXCL12 in the olfactory stem cell niche adjusts neurogenesis. We identify subepithelial tissue and sustentacular cells, the olfactory glia, as main CXCL12 sources. Lamina propria-derived CXCL12 accumulates on quiescent gliogenic stem cells via heparan sulfate. Additionally, CXCL12 is secreted within the olfactory epithelium by sustentacular cells. Both sustentacular-cell-derived and lamina propria-derived CXCL12 are required for CXCR4 activation. ACKR3, a high-affinity CXCL12 scavenger, is expressed by mature glial cells and titrates CXCL12. The accurate adjustment of CXCL12 by ACKR3 is critical for CXCR4-dependent proliferation of neuronal stem cells and for proper lineage progression. Overall, these findings establish precise regulation of CXCL12 by glia cells as a prerequisite for CXCR4-dependent neurogenesis and identify ACKR3 as a scavenger influencing tissue homeostasis beyond embryonic development.
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spelling pubmed-104865852023-09-09 Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12 Dietz, André Senf, Katja Karius, Julia Stumm, Ralf Neuhaus, Eva Maria Cells Article Olfaction depends on lifelong production of sensory neurons from CXCR4 expressing neurogenic stem cells. Signaling by CXCR4 depends on the concentration of CXCL12, CXCR4’s principal ligand. Here, we use several genetic models to investigate how regulation of CXCL12 in the olfactory stem cell niche adjusts neurogenesis. We identify subepithelial tissue and sustentacular cells, the olfactory glia, as main CXCL12 sources. Lamina propria-derived CXCL12 accumulates on quiescent gliogenic stem cells via heparan sulfate. Additionally, CXCL12 is secreted within the olfactory epithelium by sustentacular cells. Both sustentacular-cell-derived and lamina propria-derived CXCL12 are required for CXCR4 activation. ACKR3, a high-affinity CXCL12 scavenger, is expressed by mature glial cells and titrates CXCL12. The accurate adjustment of CXCL12 by ACKR3 is critical for CXCR4-dependent proliferation of neuronal stem cells and for proper lineage progression. Overall, these findings establish precise regulation of CXCL12 by glia cells as a prerequisite for CXCR4-dependent neurogenesis and identify ACKR3 as a scavenger influencing tissue homeostasis beyond embryonic development. MDPI 2023-08-28 /pmc/articles/PMC10486585/ /pubmed/37681896 http://dx.doi.org/10.3390/cells12172164 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dietz, André
Senf, Katja
Karius, Julia
Stumm, Ralf
Neuhaus, Eva Maria
Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12
title Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12
title_full Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12
title_fullStr Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12
title_full_unstemmed Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12
title_short Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12
title_sort glia cells control olfactory neurogenesis by fine-tuning cxcl12
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486585/
https://www.ncbi.nlm.nih.gov/pubmed/37681896
http://dx.doi.org/10.3390/cells12172164
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