Podoplanin is Responsible for the Distinct Blood and Lymphatic Capillaries.
Podoplanin is Responsible for the Distinct Blood and Lymphatic Capillaries.
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DOI：
10.1007/s12195-022-00730-2
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发表时间：
2022-10
影响因子：
2.8
通讯作者：
Hanjaya-Putra D
中科院分区：
文献类型：
--
作者：
Jeong DP;Hall E;Neu E;Hanjaya-Putra D
控制血液和淋巴管系统的形成对于工程组织至关重要。尽管淋巴管起源于胚胎血管，但即使它们在彼此附近发育，两者仍保留功能和生理差异。这表明存在一种以前未知的分子机制，血液（BEC）和淋巴内皮细胞（LEC）通过该机制相互识别并协调产生不同的毛细血管网络。我们利用基质胶和纤维蛋白测定来确定如何通过平足蛋白 (PDPN) 和卵泡蛋白 (FLCN) 表达改变 LEC 和 BEC 特性来控制索状结构 (CLS)。我们生成了 BECΔFLCN 和 LECΔPDPN，并观察细胞迁移以表征由于各自的敲除而导致的淋巴和血液特征损失。我们观察到 LEC 和 BEC 在基质胶和纤维蛋白凝胶中形成不同的 CLS，尽管它们彼此靠近培养。我们证实 LEC 和 BEC 不会通过旁分泌信号相互识别，因为两种细胞的增殖和迁移均不受旁分泌信号的影响。另一方面，我们发现PDPN是负责LEC-BEC识别的关键表面蛋白，缺乏PDPN的LEC变成伪BEC，反之亦然。我们还发现 FLCN 通过下调 PDPN 来维持 BEC 身份。总的来说，这些观察揭示了一种新的分子途径，LECs和BECs通过PDPN的物理接触形成不同的CLS，而PDPN又受到FLCN的调节，这对设计功能性工程组织具有重要意义。在线版本包含可在 10.1007/s12195-022-00730-2 获取的补充材料。
Controlling the formation of blood and lymphatic vasculatures is crucial for engineered tissues. Although the lymphatic vessels originate from embryonic blood vessels, the two retain functional and physiological differences even as they develop in the vicinity of each other. This suggests that there is a previously unknown molecular mechanism by which blood (BECs) and lymphatic endothelial cells (LECs) recognize each other and coordinate to generate distinct capillary networks. We utilized Matrigel and fibrin assays to determine how cord-like structures (CLS) can be controlled by altering LEC and BEC identity through podoplanin (PDPN) and folliculin (FLCN) expressions. We generated BECΔFLCN and LECΔPDPN, and observed cell migration to characterize loss lymphatic and blood characteristics due to respective knockouts. We observed that LECs and BECs form distinct CLS in Matrigel and fibrin gels despite being cultured in close proximity with each other. We confirmed that the LECs and BECs do not recognize each other through paracrine signaling, as proliferation and migration of both cells were unaffected by paracrine signals. On the other hand, we found PDPN to be the key surface protein that is responsible for LEC-BEC recognition, and LECs lacking PDPN became pseudo-BECs and vice versa. We also found that FLCN maintains BEC identity through downregulation of PDPN. Overall, these observations reveal a new molecular pathway through which LECs and BECs form distinct CLS through physical contact by PDPN which in turn is regulated by FLCN, which has important implications toward designing functional engineered tissues. The online version contains supplementary material available at 10.1007/s12195-022-00730-2.
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影响因子：
9.7
作者：
Alderfer, Laura;Hall, Eva;Hanjaya-Putra, Donny
通讯作者：
Hanjaya-Putra, Donny
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作者：
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通讯作者：
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作者：
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