Peyer's Patch M Cells Derived from Lgr5+ Stem Cells Require SpiB and Are Induced by RankL in Cultured "Miniguts"
Peyer's Patch M Cells Derived from Lgr5+ Stem Cells Require SpiB and Are Induced by RankL in Cultured "Miniguts"
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DOI：
10.1128/mcb.00434-12
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发表时间：
2012-09-01
影响因子：
5.3
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
de Lau, Wim;Kujala, Pekka;Clevers, Hans
派尔集合淋巴结由覆盖肠相关淋巴组织（GALT）的特化肠上皮组成。管腔抗原通过上皮门控细胞（所谓的M细胞）移位到达GALT。我们最近证明，肠道消化功能所需的所有上皮细胞都是由表达Lgr 5的干细胞产生的。在这里，我们表明M细胞也来自这些基于隐窝的Lgr 5干细胞。已知控制骨髓源性免疫细胞的效应子功能的Ets家族转录因子SpiB在M细胞中特异性表达。在SpiB（-/-）小鼠中，M细胞完全不存在，这以细胞自主的方式发生。已显示Tnfsf 11（RankL）可在体内诱导M细胞发育。我们表明，在肠道类器官（“小肠”）的文化，刺激与RankL诱导SpiB的表达在24小时内和其他M细胞标志物的表达随后。我们的结论是，RankL诱导的SpiB的表达是必不可少的Lgr 5干细胞衍生的上皮前体细胞发展成M细胞。
Peyer's patches consist of domains of specialized intestinal epithelium overlying gut-associated lymphoid tissue (GALT). Luminal antigens reach the GALT by translocation through epithelial gatekeeper cells, the so-called M cells. We recently demonstrated that all epithelial cells required for the digestive functions of the intestine are generated from Lgr5-expressing stem cells. Here, we show that M cells also derive from these crypt-based Lgr5 stem cells. The Ets family transcription factor SpiB, known to control effector functions of bone marrow-derived immune cells, is specifically expressed in M cells. In SpiB(-/-) mice, M cells are entirely absent, which occurs in a cell-autonomous fashion. It has been shown that Tnfsf11 (RankL) can induce M cell development in vivo. We show that in intestinal organoid ("minigut") cultures, stimulation with RankL induces SpiB expression within 24 h and expression of other M cell markers subsequently. We conclude that RankL-induced expression of SpiB is essential for Lgr5 stem cell-derived epithelial precursors to develop into M cells.