Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair.
Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair.
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DOI：
10.7554/elife.30657
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发表时间：
2018-02-06
期刊：
影响因子：
7.7
通讯作者：
Patton EE
中科院分区：
文献类型：
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作者：
Lopez-Baez JC;Simpson DJ;LLeras Forero L;Zeng Z;Brunsdon H;Salzano A;Brombin A;Wyatt C;Rybski W;Huitema LFA;Dale RM;Kawakami K;Englert C;Chandra T;Schulte-Merker S;Hastie ND;Patton EE
退行性脊柱疾病的再生治疗需要鉴定可以减缓并可能逆转退行性过程的细胞。在这里，我们确定了一个意想不到的伤口特异性脊索鞘细胞亚群，表达Wilms肿瘤（WT）1b损伤后在斑马鱼。我们发现，局部损伤导致鞘细胞中的Wt 1b表达，并且Wt 1b+细胞迁移到伤口中形成塞子样结构，可能保持结构完整性。Wt 1b+鞘细胞在表达软骨和空泡基因以及抑制Wt 1b-p53转录程序方面是不同的。在伤口处，wt 1b+和entpd 5+细胞构成独立的、紧密相关的亚群。令人惊讶的是，在损伤部位的wt 1b表达甚至在发育中的椎骨中保持到成年阶段，其通过软骨中间体以非典型的方式形成。鉴于脊索细胞保留在成人椎间盘中，新亚群的鉴定可能对再生性脊柱疾病的治疗具有重要意义。
Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments.