Distinct cellular origins for serotonin-expressing and enterochromaffin-like cells in the gastric corpus.
Distinct cellular origins for serotonin-expressing and enterochromaffin-like cells in the gastric corpus.
复制标题
胃体中表达血清素和肠嗜铬样细胞的不同细胞起源。
DOI：
10.1053/j.gastro.2013.11.048
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发表时间：
2014
期刊：
影响因子：
29.4
通讯作者：
Leiter,AndrewB
中科院分区：
文献类型：
--
作者：
Li,HuiJoyce;Johnston,Brian;Aiello,Daniel;Caffrey,DanielR;Giel-Moloney,Maryann;Rindi,Guido;Leiter,AndrewB
背景与目的消化道是一个由肠内分泌细胞组成的弥漫性内分泌系统，其分泌肽或生物胺来调节消化、胰岛素分泌、食物摄入和能量稳态。胃的谱系分析显示，与消化道其他地方的肠内分泌细胞不同，胃主体中的大部分内分泌细胞并非来自表达Neurogenin3 （Neurog3）的细胞。我们的目的是从胃中分离富集的血清素分泌细胞和肠嗜铬细胞样（ECL），并阐明它们的细胞来源。方法采用神经源性分化1 （NeuroD1）和Neurog3谱系分析，检测胃组织中血清素生成细胞和ECL细胞的分化情况；ROSAtdTom、色氨酸羟化酶1 (Tph1) -青色荧光蛋白（CFP）、c-Kitwsh/wsh、Neurog3Cre；ROSAtdTommice免疫组化。我们使用荧光活化细胞分选分离出每种细胞类型进行基因表达分析。我们还对ECL细胞进行了RNA测序分析。结果表达NeuroD1的细胞既不产生血清素分泌细胞，也不产生ECL细胞。血清素分泌细胞表达许多肥大细胞基因，但不表达与内分泌分化相关的基因；它们没有在c-Kitwsh/ wsh小鼠中发育，并且用移植的骨髓细胞标记。ECL细胞的RNA测序分析显示，内分泌细胞中许多常见基因的高表达水平，包括转录因子、激素、离子通道和溶质转运蛋白，但没有骨髓细胞的标记物。结论小鼠胃主体表达血清素的细胞可能是骨髓源性粘膜肥大细胞。ECL细胞的基因表达分析表明，它们是上皮来源的内分泌细胞，不表达与肠道内分泌细胞相同的转录因子。
Background & AimsThe alimentary tract contains a diffuse endocrine system comprising enteroendocrine cells that secrete peptides or biogenic amines to regulate digestion, insulin secretion, food intake, and energy homeostasis. Lineage analysis in the stomach revealed that a significant fraction of endocrine cells in the gastric corpus did not arise from Neurogenin3 (Neurog3)-expressing cells, unlike enteroendocrine cells elsewhere in the digestive tract. We aimed to isolate enriched serotonin-secreting and enterochromaffin-like (ECL) cells from the stomach and to clarify their cellular origin.MethodsWe used Neurogenic differentiation 1 (NeuroD1) and Neurog3 lineage analysis and examined the differentiation of serotonin-producing and ECL cells in stomach tissues of NeuroD1-cre;ROSAtdTom, tryptophan hydroxylase 1 (Tph1)–cyan fluorescent protein (CFP), c-Kitwsh/wsh, and Neurog3Cre;ROSAtdTommice by immunohistochemistry. We used fluorescence-activated cell sorting to isolate each cell type for gene expression analysis. We also performed RNA sequencing analysis of ECL cells.ResultsNeither serotonin-secreting nor ECL cells of the corpus arose from cells expressing NeuroD1. Serotonin-secreting cells expressed a number of mast cell genes but not genes associated with endocrine differentiation; they did not develop in c-Kitwsh/wshmice and were labeled with transplanted bone marrow cells. RNA sequencing analysis of ECL cells revealed high expression levels of many genes common to endocrine cells, including transcription factors, hormones, ion channels, and solute transporters but not markers of bone marrow cells.ConclusionsSerotonin-expressing cells of the gastric corpus of mice appear to be bone marrow–derived mucosal mast cells. Gene expression analysis of ECL cells indicated that they are endocrine cells of epithelial origin that do not express the same transcription factors as their intestinal enteroendocrine cell counterparts.