Origin of the brush cell lineage in the mouse intestinal epithelium.
Origin of the brush cell lineage in the mouse intestinal epithelium.
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DOI：
10.1016/j.ydbio.2011.12.009
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发表时间：
2012-02-15
影响因子：
2.7
通讯作者：
Cheng H
中科院分区：
文献类型：
--
作者：
Bjerknes M;Khandanpour C;Möröy T;Fujiyama T;Hoshino M;Klisch TJ;Ding Q;Gan L;Wang J;Martín MG;Cheng H
混合祖细胞是肠道上皮干细胞启动分化程序时形成的短命多潜能细胞。克隆动力学表明，Mix通过一系列逐渐受限的祖细胞状态产生各种上皮细胞系。Mix子细胞（DOM）之间的横向抑制Notch信号被认为打破了它们最初的对称性，从而决定了DOM是调用柱状（吸收）细胞谱系程序还是粒细胞（分泌）细胞谱系程序。这是由强制Notch信号或Atoh1缺失后的粒细胞缺失所支持的。相反，抑制Notch信号或Hes1缺失后，粒细胞频率增加。因此Hes1和Atoh1之间的相互抑制被认为在DOM中实现了Notch信号驱动的决定细胞命运的二进制开关。刷状细胞（簇状细胞）是一种鲜为人知的化学感觉细胞类型，不包括在这个模型中。我们报道，在条件缺失atoh1后，刷细胞数量急剧增加，表明刷细胞的产生、决定、分化和存活都与atoh1无关。我们还报道了刷状细胞来源于表达gfi1b的祖细胞。这些和相关的结果表明，在一个模型中，最初等效的DOM祖细胞具有由转录因子Hes1、Atoh1和Gfi1b定义的三个亚稳态。横向抑制性Notch信号通常确保Hes1在两个DOM中的一个DOM中占主导地位，调用柱状谱系程序，而Atoh1或Gfi1b在另一个DOM中占主导地位，分别调用粒细胞或刷状细胞谱系程序，从而实现细胞命运决定的三重开关。
Mix progenitors are short-lived multipotential cells formed as intestinal epithelial stem cells initiate a differentiation program. Clone dynamics indicates that various epithelial cell lineages arise from Mix via a sequence of progressively restricted progenitor states. Lateral inhibitory Notch signaling between the daughters of Mix (DOM) is thought to break their initial symmetry, thereby determining whether a DOM invokes a columnar (absorptive) or granulocytic (secretory) cell lineage program. This is supported by the absence of granulocytes following enforced Notch signaling or Atoh1 deletion. Conversely, granulocytes increase in frequency following inhibition of Notch signaling or Hes1 deletion. Thus reciprocal repression between Hes1 and Atoh1 is thought to implement a Notch signaling-driven cell-fate-determining binary switch in DOM. The brush (tuft) cells, a poorly understood chemosensory cell type, are not incorporated into this model. We report that brush cell numbers increase dramatically following conditional Atoh1-deletion, demonstrating that brush cell production, determination, differentiation and survival are Atoh1-independent. We also report that brush cells are derived from Gfi1b-expressing progenitors. These and related results suggest a model in which initially equivalent DOM progenitors have three metastable states defined by the transcription factors Hes1, Atoh1, and Gfi1b. Lateral inhibitory Notch signaling normally ensures that Hes1 dominates in one of the two DOMs, invoking a columnar lineage program, while either Atoh1 or Gfi1b dominates in the other DOM, invoking a granulocytic or brush cell lineage program, respectively, and thus implementing a cell fate-determining ternary switch.
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影响因子：
2.5
作者：
Bezencon, C.;Fuerholz, A.;Damak, S.
通讯作者：
Damak, S.
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
--
作者：
CHENG, H;LEBLOND, CP
通讯作者：
LEBLOND, CP
DOI：
10.1152/ajpgi.00160.2005
发表时间：
2005-09-01
影响因子：
4.5
作者：
Bjerknes, M;Cheng, H
通讯作者：
Cheng, H