Aged Callus Skeletal Stem/Progenitor Cells Contain an Inflammatory Osteogenic Population With Increased IRF and NF-κB Pathways and Reduced Osteogenic Potential.
Aged Callus Skeletal Stem/Progenitor Cells Contain an Inflammatory Osteogenic Population With Increased IRF and NF-κB Pathways and Reduced Osteogenic Potential.
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DOI：
10.3389/fmolb.2022.806528
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
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骨骼干/祖细胞（SSPC）通过在老化中受损的骨痂中提供骨软骨前体而对骨折修复至关重要。然而，老化过程中愈伤组织SSPC的分子特征尚不清楚。在此，我们对从年轻和老年小鼠愈伤组织中分离的11，957个CD 45-CD 31-Ter 119-SSPC进行了单细胞RNA测序。结合无监督聚类、推定标记和DEG/途径分析，将主要SSPC聚类注释为成骨、增殖和脂肪形成群体。轨迹分析显示，增殖簇具有向成骨细胞和成脂细胞分化的潜能。与成骨细胞、脂肪细胞或增殖相关的基因表达升高进一步证明了单个簇的成骨/脂肪形成/增殖潜力。成骨细胞群分为管家细胞群和炎性成骨细胞群，它们在老化骨痂中分别减少和增加。大多数炎性成骨细胞群的主要调节因子属于IRF和NF-κB家族，这通过免疫染色、RT-qPCR和Western印迹分析得到证实。此外，炎性成骨细胞亚群中的细胞具有降低的成骨细胞分化能力。总之，我们确定了愈伤组织SSPC中的3个主要簇，证实了它们的异质性，重要的是，增加了IRF/NF-κ B介导的炎性成骨细胞群，降低了老化细胞的成骨潜力。
Skeletal stem/progenitor cells (SSPCs) are critical for fracture repair by providing osteo-chondro precursors in the callus, which is impaired in aging. However, the molecular signatures of callus SSPCs during aging are not known. Herein, we performed single-cell RNA sequencing on 11,957 CD45-CD31-Ter119- SSPCs isolated from young and aged mouse calluses. Combining unsupervised clustering, putative makers, and DEGs/pathway analyses, major SSPC clusters were annotated as osteogenic, proliferating, and adipogenic populations. The proliferating cluster had a differentiating potential into osteogenic and adipogenic lineages by trajectory analysis. The osteoblastic/adipogenic/proliferating potential of individual clusters was further evidenced by elevated expression of genes related to osteoblasts, adipocytes, or proliferation. The osteogenic cluster was sub-clustered into house-keeping and inflammatory osteogenic populations that were decreased and increased in aged callus, respectively. The majority of master regulators for the inflammatory osteogenic population belong to IRF and NF-κB families, which was confirmed by immunostaining, RT-qPCR, and Western blot analysis. Furthermore, cells in the inflammatory osteogenic sub-cluster had reduced osteoblast differentiation capacity. In conclusion, we identified 3 major clusters in callus SSPCs, confirming their heterogeneity and, importantly, increased IRF/NF-κB-mediated inflammatory osteogenic population with decreased osteogenic potential in aged cells.
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影响因子：
20.1
作者：
Drechsler M;de Jong R;Rossaint J;Viola JR;Leoni G;Wang JM;Grommes J;Hinkel R;Kupatt C;Weber C;Döring Y;Zarbock A;Soehnlein O
通讯作者：
Soehnlein O
影响因子：
7.3
作者：
Astarita JL;Acton SE;Turley SJ
通讯作者：
Turley SJ
影响因子：
4
作者：
Frazão JB;Thain A;Zhu Z;Luengo M;Condino-Neto A;Newburger PE
通讯作者：
Newburger PE
影响因子：
5.2
作者：
Duque, Gustavo;Huang, Dao Chao;Kremer, Richard
通讯作者：
Kremer, Richard
DOI：
10.1073/pnas.192460799
发表时间：
2002-10-01
影响因子：
11.1
作者：
Bergo, MO;Gavino, B;Young, SG
通讯作者：
Young, SG