Human Adult Fibroblast-like Synoviocytes and Articular Chondrocytes Exhibit Prominent Overlap in Their Transcriptomic Signatures.
Human Adult Fibroblast-like Synoviocytes and Articular Chondrocytes Exhibit Prominent Overlap in Their Transcriptomic Signatures.
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成人成纤维细胞样滑膜细胞和关节软骨细胞在其转录组学特征中表现出显著的重叠。
DOI：
10.1002/acr2.11255
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发表时间：
2021-06
影响因子：
3.4
通讯作者：
Bhattaram P
中科院分区：
文献类型：
--
作者：
Jones K;Angelozzi M;Gangishetti U;Haseeb A;de Charleroy C;Lefebvre V;Bhattaram P
成纤维细胞样滑膜细胞（FLS）和关节软骨细胞（AC）来源于共同的胚胎前体细胞库。目前认为，它们参与了很大程度上不同的分化程序，以建立滑膜和关节软骨，并在一生中保持健康的组织。我们通过深入表征和比较它们的转录组属性来测试这一假设。我们使用批量RNA测序测定分析了健康成人新鲜分离的AC、滑膜、原代FLS和真皮成纤维细胞的转录组，并下载了新鲜分离的人FLS的已发表单细胞RNA测序数据。我们整合了所有数据以定义细胞特异性特征，并通过人类样本的定量逆转录PCR和小鼠关节切片的RNA杂交验证了结果。我们确定了212 AC和168 FLS标志物的基础上的排他性或丰富的表达在任一细胞和294 AC/FLS标志物的基础上，在两种细胞中的相似表达。AC标志物包括关节特异性和泛软骨基因。FLS和AC/FLS标志物分别具有37和55个关节特异性基因，以及131和239个泛成纤维细胞基因。这些特征包括许多以前未识别的具有潜在重要关节特异性作用的标志物。AC/FLS标志物在所有FLS和AC亚群中的表达模式重叠，表明它们在所有AC和FLS亚群中而不是在离散AC和FLS亚群中满足关节特异性。这项研究拓宽了知识，并确定了人类成人AC和FLS转录组签名的突出重叠。它还提供了数据资源，以帮助进一步破译关节稳态和退化的机制，并改善再生治疗工程组织的质量控制。
Fibroblast‐like synoviocytes (FLS) and articular chondrocytes (AC) derive from a common pool of embryonic precursor cells. They are currently believed to engage in largely distinct differentiation programs to build synovium and articular cartilage and maintain healthy tissues throughout life. We tested this hypothesis by deeply characterizing and comparing their transcriptomic attributes. We profiled the transcriptomes of freshly isolated AC, synovium, primary FLS, and dermal fibroblasts from healthy adult humans using bulk RNA sequencing assays and downloaded published single‐cell RNA sequencing data from freshly isolated human FLS. We integrated all data to define cell‐specific signatures and validated findings with quantitative reverse transcription PCR of human samples and RNA hybridization of mouse joint sections. We identified 212 AC and 168 FLS markers on the basis of exclusive or enriched expression in either cell and 294 AC/FLS markers on the basis of similar expression in both cells. AC markers included joint‐specific and pan‐cartilaginous genes. FLS and AC/FLS markers featured 37 and 55 joint‐specific genes, respectively, and 131 and 239 pan‐fibroblastic genes, respectively. These signatures included many previously unrecognized markers with potentially important joint‐specific roles. AC/FLS markers overlapped in their expression patterns among all FLS and AC subpopulations, suggesting that they fulfill joint‐specific properties in all, rather than in discrete, AC and FLS subpopulations. This study broadens knowledge and identifies a prominent overlap of the human adult AC and FLS transcriptomic signatures. It also provides data resources to help further decipher mechanisms underlying joint homeostasis and degeneration and to improve the quality control of tissues engineered for regenerative treatments.
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DOI：
10.1016/j.cub.2017.04.057
发表时间：
2017-06-05
期刊：
Current biology : CB
影响因子：
--
作者：
Marchant TW;Johnson EJ;McTeir L;Johnson CI;Gow A;Liuti T;Kuehn D;Svenson K;Bermingham ML;Drögemüller M;Nussbaumer M;Davey MG;Argyle DJ;Powell RM;Guilherme S;Lang J;Ter Haar G;Leeb T;Schwarz T;Mellanby RJ;Clements DN;Schoenebeck JJ
通讯作者：
Schoenebeck JJ
DOI：
10.1002/art.40386
发表时间：
2018-03
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Bhattaram P;Muschler G;Wixler V;Lefebvre V
通讯作者：
Lefebvre V
DOI：
10.1038/nrrheum.2012.15
发表时间：
2012-02-07
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Killock, David
通讯作者：
Killock, David
影响因子：
4.6
作者：
Liu, Chia-Feng;Angelozzi, Marco;Lefebvre, Veronique
通讯作者：
Lefebvre, Veronique
影响因子：
--
作者：
Chen, Xuesong;Macica, Carolyn M.;Nasiri, Ali;Broadus, Arthur E.
通讯作者：
Broadus, Arthur E.