Generation of specialized blood vessels via lymphatic transdifferentiation.
Generation of specialized blood vessels via lymphatic transdifferentiation.
复制标题
通过淋巴转分化生成专门的血管。
DOI：
10.1038/s41586-022-04766-2
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发表时间：
2022-06
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞的谱系和发育轨迹是细胞特性的关键决定因素。在血管系统中，血管内皮细胞(ECs)和淋巴管(LV)分化和专门化，以满足每个器官的独特生理需求。虽然LV被证明来自多种细胞来源，但淋巴内皮细胞(LECs)并不知道能产生其他类型的细胞。在这里，我们使用斑马鱼肛鳍(AF)内皮细胞的重复成像和谱系追踪，从早期发育到成年，揭示了LEC通过转分化形成特殊血管的意想不到的机制。此外，我们还证明了来自淋巴管和血液内皮细胞的房颤血管导致了成年生物体的功能差异，揭示了细胞个体发育和功能之间的联系。我们进一步使用scRNA-seq来表征转分化过程中涉及的不同细胞群体和过渡状态。最后，我们发现，与正常发育相似，在AF再生过程中，血管系统是从淋巴管重新获得的，这表明成年鱼的LECs保持了生成血液ECs的能力和可塑性。总体而言，我们的工作强调了通过LEC转分化形成血管的新的先天机制，并为细胞个体发育和ECs功能之间的联系提供了体内证据。
The lineage and developmental trajectory of a cell are key determinants of cellular identity. In the vascular system, endothelial cells (ECs) of blood and lymphatic vessels (LVs) differentiate and specialize to cater the unique physiological demands of each organ. While LVs were shown to derive from multiple cellular origins, lymphatic ECs (LECs) are not known to generate other cell-types. Here, we use recurrent imaging and lineage-tracing of ECs in zebrafish anal fins (AF), from early development through adulthood, to uncover an unexpected mechanism of specialized blood vessel formation through transdifferentiation of LECs. Moreover, we demonstrate that deriving AF vessels from lymphatic vs. blood ECs results in functional differences in the adult organism, uncovering a link between cell ontogeny and functionality. We further use scRNA-seq to characterize the different cellular populations and transition states involved in the transdifferentiation process. Finally, we show that akin to normal development, the vasculature is re-derived from lymphatics during AF regeneration, demonstrating that LECs in adult fish retain both potency and plasticity for generating blood ECs. Overall, our work highlights a new innate mechanism of blood vessel formation through LEC transdifferentiation, and provides in vivo evidence for a link between cell ontogeny and functionality in ECs.
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影响因子：
32.4
作者：
Hoffman D;Tevet Y;Trzebanski S;Rosenberg G;Vainman L;Solomon A;Hen-Avivi S;Ben-Moshe NB;Avraham R
通讯作者：
Avraham R
影响因子：
3.4
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影响因子：
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