- Title
- Single-cell RNA transcriptomic analysis identifies Creb5 and CD11b-DCs as regulator of asthma exacerbations
- Creator
- Liu, Xiaojie; Netto, Keilah G.; Foster, Paul S.; Li, Fuguang; Yang, Ming; Sokulsky, Leon A.; Zhou, Lujia; Xu, Huisha; Liu, Chi; Wang, Ming; Wang, Huaqi; Li, Hui; Zhang, Guojun
- Relation
- Mucosal Immunology Vol. 15, Issue 6, p. 1363-1374
- Publisher Link
- http://dx.doi.org/10.1038/s41385-022-00556-1
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2022
- Description
- Immune responses that result in asthma exacerbation are associated with allergen or viral exposure. Identification of common immune factors will be beneficial for the development of uniformed targeted therapy. We employed a House Dust Mite (HDM) mouse model of asthma and challenged allergic HDM mice with allergens (HDM, cockroach extract (CRE)) or respiratory syncytial virus (RSV). Purified lung immune cells underwent high-dimensional single-cell RNA deep sequencing (scRNA-seq) to generate an RNA transcriptome. Gene silencing with siRNA was employed to confirm the efficacy of scRNA-seq analysis. scRNA-seq UMAP analysis portrayed an array of cell markers within individual immune clusters. SCENIC R analysis showed an increase in regulon number and activity in CD11b- DC cells. Analysis of conserved regulon factors further identified Creb5 as a shared regulon between the exacerbation groups. Creb5 siRNAs attenuated HDM, CRE or RSV-induced asthma exacerbation. scRNA-seq multidimensional analysis of immune clusters identified gene pathways that were conserved between the exacerbation groups. We propose that these analyses provide a strong framework that could be used to identify specific therapeutic targets in multifaceted pathologies.
- Subject
- allergens; animals; asthma; respiratory syncytial viruses; single-cell analysis; RNA; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1480608
- Identifier
- uon:50541
- Identifier
- ISSN:1933-0219
- Rights
- The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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