Differentially expressed chaperone genes reveal a stress response required for unidirectional regeneration in the basal chordate Ciona.

Differentially expressed chaperone genes reveal a stress response required for unidirectional regeneration in the basal chordate Ciona.
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DOI:
10.1186/s12915-023-01633-y
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发表时间:
2023-06-26
期刊:
影响因子:
5.4
通讯作者:
Ma, Li
Ma, Li
中科院分区:
生物学2区
文献类型:
--
作者:
Jeffery, William R.;Li, Bo;Ng, Mandy;Li, Lianwei;Goricki, Spela;Ma, Li

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Unidirectional regeneration in the basal chordate Ciona intestinalis involves the proliferation of adult stem cells residing in the branchial sac vasculature and the migration of progenitor cells to the site of distal injury.然而,海鞘体被一分为二后,再生发生在近端,而不是远端碎片,即使后者包括含有干细胞的部分鳃囊。对再生动物分离的鳃囊进行转录组测序和组装,该信息用于深入了解远端身体碎片是否缺乏再生。我们鉴定了 1149 个差异表达基因,通过加权基因相关网络分析将其分为两个主要模块,一个主要由与再生相关的上调基因组成,另一个仅由与代谢和稳态过程相关的下调基因组成。 hsp70、dnaJb4 和 bag3 基因属于上调程度最高的基因,预计会在 HSP70 伴侣系统中相互作用。 HSP70 伴侣基因的上调得到了验证,并且在先前鉴定为干细胞和祖细胞的 BS 脉管系统细胞中也证实了它们的表达。 siRNA 介导的基因敲低表明,祖细胞靶向和远端再生需要 hsp70 和 dnaJb4,但 bag3 不需要。然而,hsp70 和 dnaJb4 在远端片段的鳃囊脉管系统中均未强烈表达,这意味着不存在应激反应。远端身体碎片的热休克处理激活了指示应激反应的 hsp70 和 dnaJb4 表达,诱导鳃囊脉管系统细胞增殖,并促进远端再生。远端损伤后,鳃囊脉管系统中的伴侣系统基因 hsp70、dnaJb4 和 bag3 显着上调,定义了对再生至关重要的应激反应。远端碎片不存在应激反应,但可以通过热休克诱导,热休克激活鳃囊脉管系统中的细胞分裂并促进远端再生。这项研究证明了应激反应对于基底脊索动物干细胞激活和再生的重要性,这可能对理解包括脊椎动物在内的其他动物的有限再生活动具有影响。在线版本包含可在 10.1186/s12915-023-01633-y 获取的补充材料。
Unidirectional regeneration in the basal chordate Ciona intestinalis involves the proliferation of adult stem cells residing in the branchial sac vasculature and the migration of progenitor cells to the site of distal injury. However, after the Ciona body is bisected, regeneration occurs in the proximal but not in the distal fragments, even if the latter include a part of the branchial sac with stem cells. A transcriptome was sequenced and assembled from the isolated branchial sacs of regenerating animals, and the information was used to provide insights into the absence of regeneration in distal body fragments. We identified 1149 differentially expressed genes, which were separated into two major modules by weighted gene correlation network analysis, one consisting of mostly upregulated genes correlated with regeneration and the other consisting of only downregulated genes associated with metabolism and homeostatic processes. The hsp70, dnaJb4, and bag3 genes were among the highest upregulated genes and were predicted to interact in an HSP70 chaperone system. The upregulation of HSP70 chaperone genes was verified and their expression confirmed in BS vasculature cells previously identified as stem and progenitor cells. siRNA-mediated gene knockdown showed that hsp70 and dnaJb4, but not bag3, are required for progenitor cell targeting and distal regeneration. However, neither hsp70 nor dnaJb4 were strongly expressed in the branchial sac vasculature of distal fragments, implying the absence of a stress response. Heat shock treatment of distal body fragments activated hsp70 and dnaJb4 expression indicative of a stress response, induced cell proliferation in branchial sac vasculature cells, and promoted distal regeneration. The chaperone system genes hsp70, dnaJb4, and bag3 are significantly upregulated in the branchial sac vasculature following distal injury, defining a stress response that is essential for regeneration. The stress response is absent from distal fragments, but can be induced by a heat shock, which activates cell division in the branchial sac vasculature and promotes distal regeneration. This study demonstrates the importance of a stress response for stem cell activation and regeneration in a basal chordate, which may have implications for understanding the limited regenerative activities in other animals, including vertebrates. The online version contains supplementary material available at 10.1186/s12915-023-01633-y.
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发表时间: 2009-12-15
影响因子: 2.2
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