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Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis
Type I interferon (IFN-1) regulates gene expression and hematopoiesis both during development and in response to inflammatory stress. We previously showed that during development in mice, hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) induce IFN-1 target genes shortly before birt...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250919/ https://www.ncbi.nlm.nih.gov/pubmed/36724510 http://dx.doi.org/10.1182/bloodadvances.2022008595 |
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author | Li, Yanan Yang, Wei Wang, Helen C. Patel, Riddhi M. Casey, Emily B. Denby, Elisabeth Magee, Jeffrey A. |
author_facet | Li, Yanan Yang, Wei Wang, Helen C. Patel, Riddhi M. Casey, Emily B. Denby, Elisabeth Magee, Jeffrey A. |
author_sort | Li, Yanan |
collection | PubMed |
description | Type I interferon (IFN-1) regulates gene expression and hematopoiesis both during development and in response to inflammatory stress. We previously showed that during development in mice, hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) induce IFN-1 target genes shortly before birth. This coincides with the onset of a transition to adult hematopoiesis, and it drives the expression of genes associated with antigen presentation. However, it is not clear whether perinatal IFN-1 modulates hematopoietic output, as has been observed in contexts of inflammation. We have characterized hematopoiesis at several different stages of blood formation, from HSCs to mature blood cells, and found that loss of the IFN-1 receptor (IFNAR1) leads to depletion of several phenotypic HSC and MPP subpopulations in neonatal and juvenile mice. Committed lymphoid and myeloid progenitor populations expand simultaneously. These changes had a surprisingly little effect on the production of more differentiated blood cells. Cellular indexing of transcriptomes and epitopes by sequencing resolved the discrepancy between the extensive changes in progenitor numbers and modest changes in hematopoiesis, revealing stability in most MPP populations in Ifnar1-deficient neonates when the populations were identified based on gene expression rather than surface marker phenotype. Thus, basal IFN-1 signaling has only modest effects on hematopoiesis. Discordance between transcriptionally and phenotypically defined MPP populations may affect interpretations of how IFN-1 shapes hematopoiesis in other contexts, such as aging or inflammation. |
format | Online Article Text |
id | pubmed-10250919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-102509192023-06-10 Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis Li, Yanan Yang, Wei Wang, Helen C. Patel, Riddhi M. Casey, Emily B. Denby, Elisabeth Magee, Jeffrey A. Blood Adv Hematopoiesis and Stem Cells Type I interferon (IFN-1) regulates gene expression and hematopoiesis both during development and in response to inflammatory stress. We previously showed that during development in mice, hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) induce IFN-1 target genes shortly before birth. This coincides with the onset of a transition to adult hematopoiesis, and it drives the expression of genes associated with antigen presentation. However, it is not clear whether perinatal IFN-1 modulates hematopoietic output, as has been observed in contexts of inflammation. We have characterized hematopoiesis at several different stages of blood formation, from HSCs to mature blood cells, and found that loss of the IFN-1 receptor (IFNAR1) leads to depletion of several phenotypic HSC and MPP subpopulations in neonatal and juvenile mice. Committed lymphoid and myeloid progenitor populations expand simultaneously. These changes had a surprisingly little effect on the production of more differentiated blood cells. Cellular indexing of transcriptomes and epitopes by sequencing resolved the discrepancy between the extensive changes in progenitor numbers and modest changes in hematopoiesis, revealing stability in most MPP populations in Ifnar1-deficient neonates when the populations were identified based on gene expression rather than surface marker phenotype. Thus, basal IFN-1 signaling has only modest effects on hematopoiesis. Discordance between transcriptionally and phenotypically defined MPP populations may affect interpretations of how IFN-1 shapes hematopoiesis in other contexts, such as aging or inflammation. The American Society of Hematology 2023-02-04 /pmc/articles/PMC10250919/ /pubmed/36724510 http://dx.doi.org/10.1182/bloodadvances.2022008595 Text en © 2023 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. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Hematopoiesis and Stem Cells Li, Yanan Yang, Wei Wang, Helen C. Patel, Riddhi M. Casey, Emily B. Denby, Elisabeth Magee, Jeffrey A. Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
title | Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
title_full | Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
title_fullStr | Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
title_full_unstemmed | Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
title_short | Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
title_sort | basal type i interferon signaling has only modest effects on neonatal and juvenile hematopoiesis |
topic | Hematopoiesis and Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250919/ https://www.ncbi.nlm.nih.gov/pubmed/36724510 http://dx.doi.org/10.1182/bloodadvances.2022008595 |
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