Apoptosis is a generator of Wnt-dependent regeneration and homeostatic cell renewal in the ascidian Ciona.

Apoptosis is a generator of Wnt-dependent regeneration and homeostatic cell renewal in the ascidian Ciona.
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细胞凋亡是海鞘中Wnt依赖性再生和稳态细胞更新的发生器。

DOI:
10.1242/bio.058526
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发表时间:
2021-04-15
期刊:
影响因子:
2.4
通讯作者:
Gorički Š
Gorički Š
中科院分区:
生物学4区
文献类型:
--
作者:
Jeffery WR;Gorički Š

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在海鞘中,基本身体部分再生远端结构,但远端身体部分不能取代基本结构。再生涉及颧囊中的成体干细胞的活动,这些干细胞增殖并产生用于组织和器官替代的迁移性祖细胞。颧囊来源的干细胞在体内平衡生长期间也会补充咽裂内的循环细胞。损伤部位的细胞凋亡在再生早期发生,在动态平衡生长期间持续发生在咽裂中。Caspase 1抑制剂、caspase 3抑制剂或PAN-caspase抑制剂Z-VAD-FMK处理可阻断细胞凋亡,阻止再生,并抑制鳃囊的生长和功能。药理学筛选和siRNA介导的基因敲除表明,再生需要规范的Wnt信号。WNT3a蛋白挽救了半胱氨酸天冬氨酸氨基转移酶阻止的再生和鳃囊的生长。抑制细胞凋亡不影响颧囊干细胞的增殖,但阻止了祖细胞的存活。在中体一分为二后,尽管两个片段都含有部分鳃囊,但仅在再生的基底部片段中发生了细胞凋亡,这表明伤口处的细胞凋亡是单侧的,颧囊干细胞的存在不足以再生。结果表明,依赖于细胞凋亡的Wnt信号介导了Ciona的再生和动态平衡生长。摘要:在Ciona中,细胞凋亡诱导Wnt依赖的再生和动态平衡细胞更新。细胞凋亡是干细胞生存所必需的,在不能再生的身体部位不存在,这表明细胞在不对称再生中起作用。
In the ascidian Ciona intestinalis, basal body parts regenerate distal structures but distal body parts do not replace basal structures. Regeneration involves the activity of adult stem cells in the branchial sac, which proliferate and produce migratory progenitor cells for tissue and organ replacement. Branchial sac-derived stem cells also replenish recycling cells lining the pharyngeal fissures during homeostatic growth. Apoptosis at injury sites occurs early during regeneration and continuously in the pharyngeal fissures during homeostatic growth. Caspase 1 inhibitor, caspase 3 inhibitor, or pan-caspase inhibitor Z-VAD-FMK treatment blocked apoptosis, prevented regeneration, and suppressed branchial sac growth and function. A pharmacological screen and siRNA-mediated gene knockdown indicated that regeneration requires canonical Wnt signaling. Wnt3a protein rescued both caspase-blocked regeneration and branchial sac growth. Inhibition of apoptosis did not affect branchial sac stem cell proliferation but prevented the survival of progenitor cells. After bisection across the mid-body, apoptosis occurred only in the regenerating basal fragments, although both fragments contained a part of the branchial sac, suggesting that apoptosis is unilateral at the wound site and the presence of branchial sac stem cells is insufficient for regeneration. The results suggest that apoptosis-dependent Wnt signaling mediates regeneration and homeostatic growth in Ciona. Summary: Apoptosis induces Wnt-dependent regeneration and homeostatic cell renewal in Ciona. Apoptosis is required for stem cell survival and is absent in non-regenerating body parts, suggesting a role in asymmetrical regeneration.
DOI: 10.1038/cdd.2017.37
发表时间: 2017-08
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