Asymmetric stem-cell divisions define the architecture of human oesophageal epithelium
Asymmetric stem-cell divisions define the architecture of human oesophageal epithelium
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DOI：
10.1016/s0960-9822(00)00803-4
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发表时间：
2000-11-16
期刊：
影响因子：
9.2
通讯作者：
Watt, FM
中科院分区：
文献类型：
--
作者：
Seery, JP;Watt, FM
尽管具有重要的临床意义，但人们对人食管上皮的干细胞区室知之甚少[1,2]。上皮基底层由两个不同的区域组成，一个覆盖在支持结缔组织（PBL）的乳头上，另一个覆盖在乳头间带（IBL）[3]上。在检查食管基底层时，我们发现在IBL中增殖细胞很少见。很大比例的有丝分裂是不对称的，产生一个基基子代和一个基上分化子代。在PBL中，有丝分裂更频繁且主要对称。IBL的特点是低表达β 1整合素和高表达β 2层粘连蛋白链。通过将荧光激活细胞分选（FACS）与体外克隆分析相结合，我们获得了IBL富集干细胞的证据。在剥离的食管结缔组织上重建正常食管上皮，其分裂不对称。相反，皮肤结缔组织不对称分裂，上皮形成类似表皮。我们认为位于IBL中的干细胞响应基底膜的提示，通过不对称分裂产生分化子细胞。到目前为止，干细胞在分层鳞状上皮中的命运被认为主要是通过群体不对称来实现的[4-6]。
In spite of its clinical importance, little is known about the stem-cell compartment of the human oesophageal epithelium [1,2]. The epithelial basal layer consists of two distinct zones, one overlying the papillae of the supporting connective tissue (PBL) and the other covering the interpapillary zone (IBL) [3]. In examining the oesophageal basal layer, we found that proliferating cells were rare in the IBL. and a high proportion of mitoses were asymmetrical, giving rise to one basal daughter and one suprabasal, differentiating daughter. In the PBL, mitoses were more frequent and predominantly symmetrical. The IBL was characterised by low expression of beta1 integrins and high expression of the beta2 laminin chain. By combining fluorescence-activated cell sorting (FACS) with in vitro clonal analysis, we obtained evidence that the IBL is enriched for stem cells. A normal oesophageal epithelium with asymmetric divisions was reconstituted on denuded oesophageal connective tissue. In contrast, asymmetric divisions were not sustained on skin connective tissue, and the epithelium formed resembled epidermis. We propose that stem cells located in the IBL give rise to differentiating daughters through asymmetric divisions in response to cues from the underlying basement membrane. Until now, stem-cell fate in stratified squamous epithelia was believed to be achieved largely through populational asymmetry [4-6].