Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme

Platelet-derived growth factor receptor alpha (PDGFR-α) activity is crucial in the process of dental and periodontal mesenchyme regeneration facilitated by autologous platelet concentrates (APCs), such as platelet-rich fibrin (PRF), platelet-rich plasma (PRP) and concentrated growth factors (CGF), a...

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Main Authors: Xue Yang, Chuyi Han, Changhao Yu, Bin Zhou, Ling Ye, Feifei Li, Fanyuan Yu
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-12-01
Series:eLife
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Online Access:https://elifesciences.org/articles/100173
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author Xue Yang
Chuyi Han
Changhao Yu
Bin Zhou
Ling Ye
Feifei Li
Fanyuan Yu
author_facet Xue Yang
Chuyi Han
Changhao Yu
Bin Zhou
Ling Ye
Feifei Li
Fanyuan Yu
author_sort Xue Yang
collection DOAJ
description Platelet-derived growth factor receptor alpha (PDGFR-α) activity is crucial in the process of dental and periodontal mesenchyme regeneration facilitated by autologous platelet concentrates (APCs), such as platelet-rich fibrin (PRF), platelet-rich plasma (PRP) and concentrated growth factors (CGF), as well as by recombinant PDGF drugs. However, it is largely unclear about the physiological patterns and cellular fate determinations of PDGFR-α+ cells in the homeostasis maintaining of adult dental and periodontal mesenchyme. We previously identified NFATc1 expressing PDGFR-α+ cells as a subtype of skeletal stem cells (SSCs) in limb bone in mice, but their roles in dental and periodontal remain unexplored. To this end, in the present study we investigated the spatiotemporal atlas of NFATc1+ and PDGFR-α+ cells residing in dental and periodontal mesenchyme in mice, their capacity for progeny cell generation, and their inclusive, exclusive and hierarchical relations in homeostasis. We utilized CRISPR/Cas9-mediated gene editing to generate two dual recombination systems, which were Cre-loxP and Dre-rox combined intersectional and exclusive reporters respectively, to concurrently demonstrate the inclusive, exclusive, and hierarchical distributions of NFATc1+ and PDGFR-α+ cells and their lineage commitment. By employing the state-of-the-art transgenic lineage tracing techniques in cooperating with tissue clearing-based advanced imaging and three-dimensional slices reconstruction, we systematically mapped the distribution atlas of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme and tracked their in vivo fate trajectories in mice. Our findings extend current understanding of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme homeostasis, and furthermore enhance our comprehension of their sustained therapeutic impact for future clinical investigations.
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spelling doaj-art-48b7438df8974cc1ad78f52e493c893d2024-12-20T13:06:41ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.100173Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchymeXue Yang0Chuyi Han1Changhao Yu2Bin Zhou3Ling Ye4Feifei Li5Fanyuan Yu6https://orcid.org/0000-0002-6879-3508State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaCenter for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaPlatelet-derived growth factor receptor alpha (PDGFR-α) activity is crucial in the process of dental and periodontal mesenchyme regeneration facilitated by autologous platelet concentrates (APCs), such as platelet-rich fibrin (PRF), platelet-rich plasma (PRP) and concentrated growth factors (CGF), as well as by recombinant PDGF drugs. However, it is largely unclear about the physiological patterns and cellular fate determinations of PDGFR-α+ cells in the homeostasis maintaining of adult dental and periodontal mesenchyme. We previously identified NFATc1 expressing PDGFR-α+ cells as a subtype of skeletal stem cells (SSCs) in limb bone in mice, but their roles in dental and periodontal remain unexplored. To this end, in the present study we investigated the spatiotemporal atlas of NFATc1+ and PDGFR-α+ cells residing in dental and periodontal mesenchyme in mice, their capacity for progeny cell generation, and their inclusive, exclusive and hierarchical relations in homeostasis. We utilized CRISPR/Cas9-mediated gene editing to generate two dual recombination systems, which were Cre-loxP and Dre-rox combined intersectional and exclusive reporters respectively, to concurrently demonstrate the inclusive, exclusive, and hierarchical distributions of NFATc1+ and PDGFR-α+ cells and their lineage commitment. By employing the state-of-the-art transgenic lineage tracing techniques in cooperating with tissue clearing-based advanced imaging and three-dimensional slices reconstruction, we systematically mapped the distribution atlas of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme and tracked their in vivo fate trajectories in mice. Our findings extend current understanding of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme homeostasis, and furthermore enhance our comprehension of their sustained therapeutic impact for future clinical investigations.https://elifesciences.org/articles/100173lineage trackinggenetic labelingmesenchymal stromal cellDental pulpperiodontal tissues
spellingShingle Xue Yang
Chuyi Han
Changhao Yu
Bin Zhou
Ling Ye
Feifei Li
Fanyuan Yu
Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme
eLife
lineage tracking
genetic labeling
mesenchymal stromal cell
Dental pulp
periodontal tissues
title Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme
title_full Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme
title_fullStr Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme
title_full_unstemmed Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme
title_short Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme
title_sort inclusive exclusive and hierarchical atlas of nfatc1 pdgfr α cells in dental and periodontal mesenchyme
topic lineage tracking
genetic labeling
mesenchymal stromal cell
Dental pulp
periodontal tissues
url https://elifesciences.org/articles/100173
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