解析淋巴之谜：研究者首次在实验室中培养淋巴组织细胞（lymphatic cells）

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Resolving a lymphatic riddle: Researchers to grow, for the first time, lymphatic cells in the lab
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$ }; [$ u! L, j; v$ cMay 20, 20158 O' J3 l1 U% W
Source:
4 o. j3 h3 x, Q  {Weizmann Institute of Science2 W* l6 w, M4 K1 p; J
Summary:
' j( O/ v- q: ]/ n9 T9 v0 ~  _For over one hundred years, scientists have debated the question of the origins of the lymphatic system -- a parallel system to the blood vessels that serves as a conduit for everything from immune cells to fat molecules to cancer cells. This debate is over, now that researchers have grown, for the first time, lymphatic cells in the lab.
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For over one hundred years, scientists have debated the question of the origins of the lymphatic system -- a parallel system to the blood vessels that serves as a conduit for everything from immune cells to fat molecules to cancer cells. This issue has now been resolved by Dr. Karina Yaniv of Weizmann Institute's Biological Regulation Department. In a study reported online in Nature, she and her team revealed how the lymphatic system develops in the embryo and for the first time managed to grow lymphatic cells in the lab.
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: T# A5 j& s& K) i* C6 JSome scientists had claimed that the lymphatic system was derived from specialized stem cells called angioblasts, whereas others had argued that it originated by the differentiation of pre-existing embryonic veins. It was the latter model that had ultimately become the accepted view.
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. K" f  Z$ T* [$ W6 _But as the research in Yaniv's lab progressed, it became clear that scientists on both sides of the argument had been right: Lymphatic cells do indeed grow from veins, but they originate from a niche within the vein that harbors angioblasts.- m1 |1 A& Q8 X

8 F# |+ V( ]5 ^2 \" R$ i6 M, M+ }' ^In the initial stages of the research project, Yaniv's team members Julian Nicenboim and Dr. Guy Malkinson obtained images of developing zebrafish embryos, whose transparent bodies make it possible to document embryonic development in real time over several days. The scientists then played the movies backward, to identify the point at which the lymphatic system began to form. To their surprise, they discovered that the cells that give rise to lymphatic vessels always originated in the same part of the embryo's major vein. In that spot, the scientists found a niche of angioblasts, those same cells that a hundred years earlier were thought to be the source of lymph vessels, but were later neglected.5 F; B( c) n0 {: j4 A& V5 p

  \0 Z( H+ [- M0 E8 RAn in-depth genetic analysis, performed with the participation of graduate students Tal Lupo and Lihee Asaf, pointed to a gene called WNT5B, which was revealed to be the factor prompting stem cells to differentiate into lymphatic cells. When postdoctoral fellow Dr. Yogev Sela added WNT5B to human embryonic stem cells, these cells indeed differentiated into lymphatic cells -- the first time such cells had been grown in the lab. "We started out by imaging zebrafish, and ended up finding a factor that makes it possible to create lymphatic cells," says Yaniv. "That's the beauty of research in developmental biology: The embryo holds the answers, and all we have to do is watch and learn."7 y5 D; l+ Q+ Q: e# Y. E
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Aside from the feat of answering the longstanding question of how the lymph system arises, understanding how it forms and develops can provide important insights into disease, from metastasis to the abnormal accumulation of lymph fluids, particularly in the wake of surgery to remove cancerous tumors.
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2 M2 s" h$ a* L. h0 ?The above story is based on materials provided by Weizmann Institute of Science. Note: Materials may be edited for content and length.! }; X6 {' u3 y/ U. [

- O/ O8 }% e; n2 b8 iJournal Reference:7 H3 h, @! q& x
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J. Nicenboim, G. Malkinson, T. Lupo, L. Asaf, Y. Sela, O. Mayseless, L. Gibbs-Bar, N. Senderovich, T. Hashimshony, M. Shin, A. Jerafi-Vider, I. Avraham-Davidi, V. Krupalnik, R. Hofi, G. Almog, J. W. Astin, O. Golani, S. Ben-Dor, P. S. Crosier, W. Herzog, N. D. Lawson, J. H. Hanna, I. Yanai, K. Yaniv. Lymphatic vessels arise from specialized angioblasts within a venous niche. Nature, 2015; DOI: 10.1038/nature14425- f' ^0 L6 C6 i( p' `) o" \

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解析淋巴之谜：研究者首次在实验室中培养淋巴组织细胞（lymphatic cells）# l0 _( }6 A8 I1 D# ^4 |# N6 M
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一百多年来，科学家一直在争论淋巴系统的起源问题。这个管道系统与血管系统并行，参与运输免疫细胞，脂肪分子和癌细胞等。现在魏兹曼研究所的研究人员的发现解决了这一争论，他们首次在实验室中培养了淋巴组织细胞。这一发现发表在最近的nature网络版中，在这篇报道中研究者揭示了淋巴管系统在胚胎中的发育过程，并且首次在实验室培养淋巴组织细胞。5 |" p+ j9 I" G+ u
一些科学家认为淋巴系统是由专门的干细胞即成血管细胞衍生来的，而另外一些科学院认为它起源于预先存在的胚胎静脉。后者逐渐被大家所公认。但是Yaniv实验室的研究结果表明双方都是对的即淋巴系统确实起源于静脉的生长，但是真正的来源是位于静脉中的niche，这些niche中存在angioblasts（成血管细胞）。
; p+ K; H! `: G在该研究项目的最初阶段，Yaniv研究团队的成员 Julian Nicenboim 和 Dr. Guy 收集斑马鱼胚胎发育的图像资料，其透明体使得研究者能够在最初的几天实时记录胚胎发育的情况。然后，他们将收集的影像资料回放，以确定淋巴管系统的起始位点。令他们吃惊的是，他们发现形成淋巴管的细胞总是来自于主静脉的同一个部分。随后，他们在那个部分发现了一个含有angioblasts的niche。这些angioblasts在一百多年前被认为是淋巴管的起源，但后来又被研究者所忽视。
3 M* D3 d, C2 V+ Q随后Tal Lupo和Lihee Asaf 进行了深入的遗传分析，发现一个叫做WNT5B的基因在干细胞分化成淋巴细胞的过程中起着关键的作业。随后Dr. Yogev Sela将这个基因（WNT5B）导入到人胚胎干细胞中，这些干细胞被诱导分化为淋巴细胞，这也是关于淋巴细胞实验室体外培养的第一次报道。 Yaniv说："We started out by imaging zebrafish, and ended up finding a factor that makes it possible to create lymphatic cells.That’s the beauty of research in developmental biology: The embryo holds the answers, and all we have to do is watch and learn.”  （这个原文很好，胚胎包含所有答案，我们要做的只是观察以及学习。）, @8 [8 C+ X2 S9 c5 a: H
这一发现不仅解答研究者一直争论的淋巴系统起源问题，了解淋巴管形成和发育的机制对于相关疾病（淋巴液异常转移和积累）的研究有着重要的意义，特别是随之而来的肿瘤切除。
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Journal Reference:1 Z( T+ [. s; p. G& p  _( g
        1        J. Nicenboim, G. Malkinson, T. Lupo, L. Asaf, Y. Sela, O. Mayseless, L. Gibbs-Bar, N. Senderovich, T. Hashimshony, M. Shin, A. Jerafi-Vider, I. Avraham-Davidi, V. Krupalnik, R. Hofi, G. Almog, J. W. Astin, O. Golani, S. Ben-Dor, P. S. Crosier, W. Herzog, N. D. Lawson, J. H. Hanna, I. Yanai, K. Yaniv. Lymphatic vessels arise from specialized angioblasts within a venous niche. Nature, 2015; DOI: 10.1038/nature14425( Y" _4 _" ], u( r: ]
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