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持久性巨噬细胞和B细胞反应的缺失抑制了墨西哥洞穴鱼的心脏再生

更新时间:2026-10-24   点击次数:22次

中文摘要:

心脏损伤后平衡的免疫反应对成功的心脏再生至关重要,但关于何种因素区分再生性反应与瘢痕性反应的认识仍然有限。墨西哥洞穴鱼 Astyanax mexicanus 提供了一个独特的比较模型,可用于在同一物种内研究心脏再生与瘢痕形成。 Astyanax 地表型鱼能够进行心脏再生,而其洞穴型帕雄(Pachón)对应群体则像人类心脏一样形成持久性瘢痕。利用单细胞转录组学和免疫扰动,我们鉴定出两种不同且大体上序贯的免疫机制,驱动地表型鱼的再生。首先,后期出现的巨噬细胞具有活跃的吞噬能力,药理学巨噬细胞清除剂Liposoma的ClodronateLiposomes抑制吞噬作用会破坏瘢痕清除和再生。其次,损伤后第7天起募集的B细胞促进心肌细胞进入有丝分裂,而用Acalabrutinib抑制B细胞会显著损害心肌细胞增殖和再生。这种依赖B细胞的机制在斑马鱼中保守存在。我们的发现揭示了两种独立的晚期免疫机制,可区分再生性与非再生性心脏修复,为增强哺乳动物心脏再生的潜在治疗策略提供了启示。


英文摘要:

A balanced immune response after cardiac injury is crucial to successful heart regeneration, but knowledge of what distinguishes a regenerative from a scarring response is still limited. The Mexican cavefish Astyanax mexicanus provides a unique comparative model to study heart regeneration and scarring within a single species. Astyanax surface-dwelling fish are capable of heart regeneration, whereas, like the human heart, their cave-dwelling Pachón counterparts form a permanent scar. Using single-cell transcriptomics and immune perturbations, we identify two distinct and largely sequential immune mechanisms driving regeneration in surface fish. First, late-present macrophages are actively phagocytic, and pharmacological inhibition of phagocytosis disrupts scar clearance and regeneration. Second, B cells recruited from 7 days post-injury promote cardiomyocyte cell progression into mitosis, and their inhibition with Acalabrutinib significantly impairs cardiomyocyte proliferation and regeneration. This B cell-dependent mechanism is conserved in zebrafish. Our findings reveal two independent late immune mechanisms distinguishing regenerative from non-regenerative cardiac repair, offering insights for potential therapeutic strategies to enhance heart regeneration in mammals.


论文信息:

论文题目:Absence of a prolonged macrophage and B cell response inhibits heart regeneration in the Mexican cavefish

期刊名称:Nature Communications

时间期卷:17, Article number:10922(2026)

在线时间:2026年9月17日

DOI: doi.org/10.1038/s41467-026-77725-4


产品信息:

货号:CP-005-005

规格:5ml+5ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes& Control Liposomes

现货:靶点科技


Clodronate Liposomes氯膦酸盐脂质体清除墨西哥洞穴鱼 Astyanax mexicanus中巨噬细胞 ,荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Nature Communications:持久性巨噬细胞和B细胞反应的缺失抑制了墨西哥洞穴鱼的心脏再生。

持久性巨噬细胞和B细胞反应的缺失抑制了墨西哥洞穴鱼的心脏再生


Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除肿瘤相关巨噬细胞的材料和方法:

Depletion of macrophages

Clodronate liposomes (5 mg Clodronate/mL) and Dil-fluorophore tagged control PBS liposomes (Liposoma, the Netherlands) were administered via intraperitoneal injection at 10 µL per fish between 7- and 14-dpci. Dil fluorescent PBS liposomes were injected from 7- to 11 dpci for 5 consecutive days to visualise affected cell populations. In a separate cohort, Clodronate and Dil-tagged PBS liposomes were mixed at 1:1 ratio and co-injected at 10 µL total per fish between 7- and 14-dpci to assess liposome uptake by targeted cell populations. Hearts were isolated at 14- and 30-dpci for RNAscope and immunostaining.


材料和方法文献截图:

持久性巨噬细胞和B细胞反应的缺失抑制了墨西哥洞穴鱼的心脏再生


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