Telocytes regulate macrophages in periodontal disease
Abstract
Telocytes (TCs) or interstitial cells are characterised in vivo by their long projections that contact other cell types. Although telocytes can be found in many different tissues including the heart1, lung2 and intestine3, their tissue-specific roles are poorly understood. Here we identify a specific cell signalling role for telocytes in the periodontium whereby telocytes regulate macrophage activity. We performed scRNA-seq and lineage tracing to identify telocytes and macrophages in mouse periodontium in homeostasis and periodontitis and carried out HGF signalling inhibition experiments using Tivantinib. We show that telocytes are quiescent in homeostasis, however, they proliferate and serve as a major source of HGF in periodontitis. Macrophages receive telocyte-derived HGF signals and shift from an M1 to a M1/M2 state. Our results reveal the source of HGF signals in periodontal tissue and provide new insights into the function of telocytes in regulating macrophage behaviour in periodontitis through HGF/Met cell signalling, that may provide a novel approach in periodontitis treatment.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE167917 and GSE160358.
-
Telocytes regulate tissue resident macrophages in periodontal diseaseNCBI Gene Expression Omnibus, GSE167917.
-
Periodontal ligament tissue periodontitisNCBI Gene Expression Omnibus, GSM5115470.
-
Cells in healthy periodontal ligamentNCBI Gene Expression Omnibus, GSE160358.
Article and author information
Author details
Funding
Chinese Academy of Agricultural Sciences (N/A)
- Paul Sharpe
NIHR BioResource (N/A)
- Paul Sharpe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bérénice A Benayoun, University of Southern California, United States
Ethics
Animal experimentation: All mouse work was approved by UK Home Office under the project license 70/7866 and P5F0A1579, approved by the KCL animal ethics committee.
Version history
- Preprint posted: June 3, 2021 (view preprint)
- Received: July 12, 2021
- Accepted: September 26, 2022
- Accepted Manuscript published: October 4, 2022 (version 1)
- Accepted Manuscript updated: October 10, 2022 (version 2)
- Version of Record published: October 17, 2022 (version 3)
Copyright
© 2022, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 772
- Page views
-
- 166
- Downloads
-
- 3
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cell Biology
Membrane contact sites (MCSs) are junctures that perform important roles including coordinating lipid metabolism. Previous studies have indicated that vacuolar fission/fusion processes are coupled with modifications in the membrane lipid composition. However, it has been still unclear whether MCS-mediated lipid metabolism controls the vacuolar morphology. Here, we report that deletion of tricalbins (Tcb1, Tcb2, and Tcb3), tethering proteins at endoplasmic reticulum (ER)–plasma membrane (PM) and ER–Golgi contact sites, alters fusion/fission dynamics and causes vacuolar fragmentation in the yeast Saccharomyces cerevisiae. In addition, we show that the sphingolipid precursor phytosphingosine (PHS) accumulates in tricalbin-deleted cells, triggering the vacuolar division. Detachment of the nucleus–vacuole junction (NVJ), an important contact site between the vacuole and the perinuclear ER, restored vacuolar morphology in both cells subjected to high exogenous PHS and Tcb3-deleted cells, supporting that PHS transport across the NVJ induces vacuole division. Thus, our results suggest that vacuolar morphology is maintained by MCSs through the metabolism of sphingolipids.
-
- Cell Biology
- Chromosomes and Gene Expression
Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of ribosomal DNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-Seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.