Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta.
Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta.
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DOI：
10.1038/s41467-021-27563-3
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发表时间：
2021-12-10
影响因子：
16.6
通讯作者：
Kalluri R
中科院分区：
文献类型：
--
作者：
Chen Y;Yang S;Lovisa S;Ambrose CG;McAndrews KM;Sugimoto H;Kalluri R
I型胶原(Col1)是哺乳动物体内含量最丰富的蛋白质。COL1占骨基质总有机成分的90%。然而，COL1在胚胎发生和骨形成中的确切细胞起源和功能贡献仍不清楚。单细胞RNA测序分析表明，Fap+细胞和Fsp1+细胞是骨骼中Col1的主要贡献者。我们建立了转基因小鼠模型，从基因上删除了不同细胞系中的col1。完整的、全身的CO1缺失会导致原肠发育失败和早期胚胎死亡。Fap+细胞中特定的CO1缺失会导致严重的骨骼缺陷，并伴有出血、水肿和产前死亡。Fsp1+细胞中特定的COL1缺失导致成年小鼠的成骨不全表型，并伴有自发性骨折和骨愈合受损。本研究展示了间充质细胞系在器官发生、骨骼发育和骨形成/修复中对Col1产生的特殊贡献，为成骨不全患者的基于细胞的治疗提供了潜在的见解。胶原蛋白是人体内含量最丰富的蛋白质。在这里，作者表明，不同类别的成纤维细胞产生独特功能的胶原蛋白，对胚胎发育和骨形成有不同的影响。
Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap+ cells and Fsp1+ cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap+ cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1+ cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta. Collagen is the most abundant protein in the human body. Here, the authors show that different classes of fibroblasts produce collagen of unique functions with different impacts on embryo development and bone formation.
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影响因子：
4.5
作者：
Bowen ME;Ayturk UM;Kurek KC;Yang W;Warman ML
通讯作者：
Warman ML
影响因子：
--
作者：
Florencio-Silva R;Sasso GR;Sasso-Cerri E;Simões MJ;Cerri PS
通讯作者：
Cerri PS
影响因子：
64.5
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
5.2
作者：
Grcevic, Danka;Pejda, Slavica;Matthews, Brya G.;Repic, Dario;Wang, Liping;Li, Haitao;Kronenberg, Mark S.;Jiang, Xi;Maye, Peter;Adams, Douglas J.;Rowe, David W.;Aguila, Hector L.;Kalajzic, Ivo
通讯作者：
Kalajzic, Ivo
影响因子：
20.3
作者：
Corada, M;Liao, F;Dejana, E
通讯作者：
Dejana, E