DYNAMICS OF EPITHELIAL-CELLS IN THE CORPUS OF THE MOUSE STOMACH .1. IDENTIFICATION OF PROLIFERATIVE CELL-TYPES AND PINPOINTING OF THE STEM-CELL

DYNAMICS OF EPITHELIAL-CELLS IN THE CORPUS OF THE MOUSE STOMACH .1. IDENTIFICATION OF PROLIFERATIVE CELL-TYPES AND PINPOINTING OF THE STEM-CELL
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DOI:
10.1002/ar.1092360202
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发表时间:
1993-06-01
期刊:
影响因子:
--
通讯作者:
LEBLOND, CP
LEBLOND, CP
中科院分区:
医学4区
文献类型:
--
作者:
KARAM, SM;LEBLOND, CP

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在最近一项对小鼠胃体上皮细胞的研究中,已经鉴定并计数了11种细胞类型(Karam和Leblond:Anat。录制。232:231-246,1992)。这些细胞的动力学将在五篇系列文章中进行研究,其中这是第一篇。本文着重研究静脉注射H-3-胸腺嘧啶核苷30分钟后处死小鼠的放射自显影标记指数测定细胞的增殖能力。此外,对增殖的细胞进行了超微结构的观察,以期找到干细胞的特征。根据其标记指数,将上皮细胞分为四类。第一种包括三种细胞类型,它们不带任何标签,因此不分裂:壁细胞或含氧细胞,命名为顶前细胞,因为它们是怀疑为壁细胞前体的未成熟细胞,以及罕见的凹陷细胞或刷状细胞。第二组由三种细胞类型组成,它们很少被标记,因此仅偶尔分裂:产酶细胞或主细胞,肠内分泌细胞,以及命名为产酶前细胞的细胞,因为它们被怀疑是产酶细胞前体。第三组包括两种细胞类型,它们总是被低程度标记,因此分裂规则,但比率低:表面粘液细胞,这里称为凹坑细胞,其标记指数为0.8%,以及粘液颈部细胞,简称为颈部细胞,1.8%。最后一组由三种标记指数高的未成熟细胞组成:无颗粒细胞,无分泌颗粒,标记指数最高,为32.4%;凹陷前细胞,有少量密集的分泌颗粒,与凹陷细胞相似,但小于凹陷细胞的24.6%;颈前细胞,少量分泌颗粒,与颈部细胞的分泌颗粒相似,但小于颈部细胞的11.3%。无颗粒细胞的超微结构研究表明,根据高尔基体的特征,它们可分为三种亚型:亚型I,由未分化的细胞组成,高尔基体反面没有前分泌小泡;亚型II,由于高尔基体反面显示出与前凹细胞相似的前分泌小泡,故命名为前凹细胞前体;亚型III,称为颈前细胞前体,其前分泌小泡与颈前细胞相似。另一方面,壁前细胞包括三种变体,每一种都可能来自不同的无颗粒亚型:变体I,没有粘液分泌颗粒,可能来自未分化的细胞;变体II,具有与前凹细胞相似的致密粘液颗粒,可能来自前凹细胞前体;变体III,具有与前颈部细胞一样的核心颗粒,可能来自前颈部细胞前体。只有未分化的无颗粒细胞才具有干细胞的特征,因此被认为是上皮的干细胞。一个基于放射自显影和形态数据的模型(图17)总结了其他未成熟细胞类型的分丝情况如下。未分化的无颗粒细胞作为干细胞自我繁殖,并产生其他三种细胞类型:1)无分泌颗粒的壁前细胞(即变体1);2)前凹细胞前体,主要产生前凹细胞,但也产生变体II的壁前细胞;3)颈前细胞的前体,主要产生颈部前细胞,但也产生变体III的壁前细胞。这些未成熟的细胞类型进一步分化为体部上皮的其他细胞将在随后的文章中进行研究。
In a recent study of the corpus epithelium in the mouse stomach, eleven cell types have been identified and enumerated (Karam and Leblond: Anat. Rec. 232:231-246, 1992). The dynamics of these cells will be examined in a series of five articles, of which this is the first. This article focuses on the proliferative ability of the cells, as measured by the labeling index in radioautographs from mice sacrificed 30 min after an intravenous injection of H-3-thymidine. Furthermore, the ultrastructure of the cells found to be proliferative was examined in the hope of finding features characteristic of stem cells.On the basis of their labeling index, the epithelial cells have been classified into four groups. The first includes three cell types which do not take up any label and accordingly are non-dividing: parietal or oxyntic cells, cells named pre-parietal as they are immature cells suspected of being parietal cell precursors, and the rare caveolated or brush cells. The second group is composed of three cell types which are only rarely labeled and, therefore, divide only occasionally: zymogenic or chief cells, entero-endocrine cells, and cells named pre-zymogenic cells as they are suspected of being zymogenic cell precursors. The third group includes two cell types which are always labeled at a low degree and, therefore, divide regularly, but at a low rate: surface mucous cells, herein called pit cells, whose labeling index is 0.8%, and mucous neck cells, simply known as neck cells, 1.8%. The final group consists of three immature cell types with high labeling indices indicating a high rate of division: granule-free cells, which are devoid of secretory granules and have the highest labeling index, 32.4%, pre-pit cells, which possess a few dense secretory granules similar to, but smaller than, those in pit cells, 24.6%, and pre-neck cells, with a small number of secretory granules similar to, but smaller than, those in neck cells, 11.3%. These three cell types, as well as pre-parietal cells, are rapidly renewed, with the turnover times estimated at 3.0 days for pre-neck and pre-parietal cells and less than 2.6 days for granule-free and pre-pit cells.Ultrastructural studies of granule-free cells reveal that they may be subdivided into three subtypes according to their Golgi features: subtype I, which consists of undifferentiated cells in which the Golgi trans face exhibits no prosecretory vesicles; subtype II, named pre-pit cell precursors because the Golgi trans face shows prosecretory vesicles similar to those in pre-pit cells; and subtype III, named pre-neck cell precursors, whose prosecretory vesicles are similar to those in pre-neck cells. On the other hand, pre-parietal cells include three variants that could each arise from a different granule-free subtype: variant I, which has no mucous secretory granules, could arise from the undifferentiated cells; variant II, which possesses dense mucous granules similar to those in pre-pit cells, could come from pre-pit cell precursors; and variant III, which has cored granules as in pre-neck cells, could come from pre-neck cell precursors.Only the undifferentiated granule-free cells have the features expected from stem cells and, therefore, are considered to be the stem cells of the epithelium. A model based on the radioautographic and morphological data (Fig. 17) summarises the filiation of the other immature cell types as follows. The undifferentiated granule-free cells as stem cells reproduce themselves and give rise to three other cell types: 1) the pre-parietal cells lacking secretory granules (i.e., variant 1); 2) the pre-pit cell precursors, which mainly give rise to pre-pit cells, but also yield the variant II pre-parietal cells; 3) the pre-neck cell precursors, which mainly give rise to pre-neck cells, but also yield the variant III pre-parietal cells. Further differentiation of these immature cell types into the other cells of the corpus epithelium is examined in the succeeding articles.