Transcription factor Tlx1 marks a subset of lymphoid tissue organizer-like mesenchymal progenitor cells in the neonatal spleen
Transcription factor Tlx1 marks a subset of lymphoid tissue organizer-like mesenchymal progenitor cells in the neonatal spleen
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DOI：
10.1038/s41598-019-56984-w
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发表时间：
2019-12
影响因子：
4.6
通讯作者：
Y. Ueno;Keiko Fujisaki;Shoko Hosoda;Yusuke Amemiya;S. Okazaki;Chihiro Notsu;C. Nishiyama;Y. Mabuchi;Y. Matsuzaki;Akihisa Oda;R. Goitsuka
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文献类型：
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作者：
Y. Ueno;Keiko Fujisaki;Shoko Hosoda;Yusuke Amemiya;S. Okazaki;Chihiro Notsu;C. Nishiyama;Y. Mabuchi;Y. Matsuzaki;Akihisa Oda;R. Goitsuka
脾由空间上不同的隔室组成，其功能，如免疫反应和清除老化的红细胞，由非造血基质细胞严格控制，这些基质细胞提供区域受限的信号，以适当地激活驻留在每个区域的造血细胞。然而，关于不同基质细胞类型的个体发育和关系的信息仍然有限。在此，我们使用了病毒示踪分析和体外间充质基质细胞分析，发现Tlx1是胚胎脾器官发生所必需的转录因子，它标记选择性地定位在脾中的新生基质细胞，并保留间充质祖细胞分化为成熟的滤泡树突状细胞、成纤维细胞网状细胞和边缘网状细胞的潜能。此外，通过建立一种新的三维细胞培养系统，能够在体外维持表达T1x1的细胞，我们发现来自淋巴毒素β受体和肿瘤坏死因子受体的信号促进这些细胞分化为表达MAdCAM-1、CCL19和CXCL13，这三种典型的功能分子由脾中不同亚群的成熟基质细胞表达。综上所述，这些发现表明，表达Tlx1的间充质祖细胞是选择性地在新生儿脾中发现的淋巴组织组织者样细胞的一个亚群。
The spleen is comprised of spatially distinct compartments whose functions, such as immune responses and removal of aged red blood cells, are tightly controlled by the non-hematopoietic stromal cells that provide regionally-restricted signals to properly activate hematopoietic cells residing in each area. However, information regarding the ontogeny and relationships of the different stromal cell types remains limited. Here we have usedin vivolineage tracing analysis andin vitromesenchymal stromal cell assays and found that Tlx1, a transcription factor essential for embryonic spleen organogenesis, marks neonatal stromal cells that are selectively localized in the spleen and retain mesenchymal progenitor potential to differentiate into mature follicular dendritic cells, fibroblastic reticular cells and marginal reticular cells. Furthermore, by establishing a novel three-dimensional cell culture system that enables maintenance of Tlx1-expressing cellsin vitro, we discovered that signals from the lymphotoxin β receptor and TNF receptor promote differentiation of these cells to express MAdCAM-1, CCL19 and CXCL13, representative functional molecules expressed by different subsets of mature stromal cells in the spleen. Taken together, these findings indicate that mesenchymal progenitor cells expressing Tlx1 are a subset of lymphoid tissue organizer-like cells selectively found in the neonatal spleen.