Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair
Abstract Plp1-lineage Schwann cells (SCs) of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing, and the abnormal plasticity of SCs would jeopardize the bone regeneration. However, how Plp1-lineage cells respond to injur...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-024-00396-8 |
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| _version_ | 1832586006534029312 |
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| author | Xin Shen Hang Zhang Zesheng Song Yangjiele Dong Xiao Ge Shenghao Jin Songsong Guo Ping Zhang Yu Fu Yuchi Zhu Na Xiao Dongmiao Wang Jie Cheng Rongyao Xu Hongbing Jiang |
| author_facet | Xin Shen Hang Zhang Zesheng Song Yangjiele Dong Xiao Ge Shenghao Jin Songsong Guo Ping Zhang Yu Fu Yuchi Zhu Na Xiao Dongmiao Wang Jie Cheng Rongyao Xu Hongbing Jiang |
| author_sort | Xin Shen |
| collection | DOAJ |
| description | Abstract Plp1-lineage Schwann cells (SCs) of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing, and the abnormal plasticity of SCs would jeopardize the bone regeneration. However, how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood. Here, by employing single-cell transcriptional profiling combined with lineage-specific tracing models, we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury. Importantly, our data demonstrated that the Sonic hedgehog (Shh) signaling was responsible for the transition process initiation, which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers. Collectively, these findings depict an injury-specific niche signal-mediated Plp1-lineage cells transition towards Gli1+ MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases. |
| format | Article |
| id | doaj-art-a07a17ce71db4870b577badb8a77ee18 |
| institution | Kabale University |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-a07a17ce71db4870b577badb8a77ee182025-01-26T12:19:48ZengNature Publishing GroupBone Research2095-62312025-01-0113111710.1038/s41413-024-00396-8Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repairXin Shen0Hang Zhang1Zesheng Song2Yangjiele Dong3Xiao Ge4Shenghao Jin5Songsong Guo6Ping Zhang7Yu Fu8Yuchi Zhu9Na Xiao10Dongmiao Wang11Jie Cheng12Rongyao Xu13Hongbing Jiang14Jiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesJiangsu Province Key Laboratory of Oral DiseasesAbstract Plp1-lineage Schwann cells (SCs) of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing, and the abnormal plasticity of SCs would jeopardize the bone regeneration. However, how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood. Here, by employing single-cell transcriptional profiling combined with lineage-specific tracing models, we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury. Importantly, our data demonstrated that the Sonic hedgehog (Shh) signaling was responsible for the transition process initiation, which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers. Collectively, these findings depict an injury-specific niche signal-mediated Plp1-lineage cells transition towards Gli1+ MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.https://doi.org/10.1038/s41413-024-00396-8 |
| spellingShingle | Xin Shen Hang Zhang Zesheng Song Yangjiele Dong Xiao Ge Shenghao Jin Songsong Guo Ping Zhang Yu Fu Yuchi Zhu Na Xiao Dongmiao Wang Jie Cheng Rongyao Xu Hongbing Jiang Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair Bone Research |
| title | Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair |
| title_full | Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair |
| title_fullStr | Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair |
| title_full_unstemmed | Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair |
| title_short | Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair |
| title_sort | enhancer driven shh signaling promotes glia to mesenchyme transition during bone repair |
| url | https://doi.org/10.1038/s41413-024-00396-8 |
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