Nestin-Expressing Precursors Give Rise to Both Endothelial as well as Nonendothelial Lymph Node Stromal Cells.

Nestin-Expressing Precursors Give Rise to Both Endothelial as well as Nonendothelial Lymph Node Stromal Cells.
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DOI:
10.4049/jimmunol.1501162
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发表时间:
2016-10-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Mebius RE
Mebius RE
中科院分区:
其他
文献类型:
--
作者:
Koning JJ;Konijn T;Lakeman KA;O'Toole T;Kenswil KJ;Raaijmakers MH;Michurina TV;Enikolopov G;Mebius RE

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在胚胎发生过程中,淋巴结通过淋巴组织诱导细胞和淋巴组织细胞(LTo)之间的密切相互作用形成。在小鼠出生后不久,专门的基质细胞亚群出现,组织淋巴结内的微环境;然而,它们的直接前体尚未被确定。在骨髓中,nestin-GFP小鼠的间充质干细胞用GFP标记,并且我们表明在发育的所有阶段,nestin+细胞存在于这些小鼠的淋巴结内。在出生当天,间充质CD 31 −和内皮CD 31 + LTo细胞都是GFP+,只有CD 31 − LTo细胞群含有间充质前体。这些CD 31 −巢蛋白+细胞存在于T和B细胞区或与成人淋巴结中的高内皮微静脉密切相关。巢蛋白+细胞的命运映射明确地揭示了巢蛋白+前体细胞对淋巴结内的间充质以及内皮基质群体的贡献。然而,出生后他莫昔芬诱导的nestin+细胞nes-creER小鼠的靶向显示,大多数内皮细胞和只有少数的非内皮细胞被标记。总的来说,我们的数据表明,巢蛋白+细胞有助于所有子集的复杂的基质人口,可以在淋巴结中发现。
During embryogenesis, lymph nodes form through intimate interaction between lymphoid tissue inducer and lymphoid tissue organizer (LTo) cells. Shortly after birth in mice, specialized stromal cell subsets arise that organize microenvironments within the lymph nodes; however, their direct precursors have not yet been identified. In the bone marrow, mesenchymal stem cells are labeled with GFP in nestin-GFP mice, and we show that during all stages of development, nestin+ cells are present within lymph nodes of these mice. At day of birth, both mesenchymal CD31− and endothelial CD31+ LTo cells were GFP+, and only the population of CD31− LTo cells contained mesenchymal precursors. These CD31−nestin+ cells are found in the T and B cell zones or in close association with high endothelial venules in adult lymph nodes. Fate mapping of nestin+ cells unambiguously revealed the contribution of nestin+ precursor cells to the mesenchymal as well as the endothelial stromal populations within lymph nodes. However, postnatal tamoxifen induced targeting of nestin+ cells in nes-creER mice showed that most endothelial cells and only a minority of the nonendothelial cells were labeled. Overall our data show that nestin+ cells contribute to all subsets of the complex stromal populations that can be found in lymph nodes.