We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologi...We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologically and functionally. Because normal enterocytes were present, we hypothesized that this patient had a developmental block in the differentiation of a common stem cell precursor for Paneth, goblet, and neuroendocrine lineages. By using antibodies to protein markers of each cell line, including some that are expressed early in the differentiation process, we aimed to study lineage development in this patient. From our data, we surmise that there may be a two-step process in lineage commitment. The stem cell may commit to an absorptive cell or a granule-containing cell. The daughter cell that is committed to the granule lineage then further commits to a goblet, enteroendocrine, or Paneth cell lineage.展开更多
应用过氧化物酶抗过氧化物酶(PAP)免疫组织化学技术,用4种哺乳动物中培育出的抗血清对草鱼、青鱼、鲤和翘嘴红鲌4种鲤科鱼的肠内分泌细胞进行免疫、组织化学的鉴别和定位.证实了高血糖素免疫活性内分泌细胞在草鱼整个肠道中均呈阳性反应...应用过氧化物酶抗过氧化物酶(PAP)免疫组织化学技术,用4种哺乳动物中培育出的抗血清对草鱼、青鱼、鲤和翘嘴红鲌4种鲤科鱼的肠内分泌细胞进行免疫、组织化学的鉴别和定位.证实了高血糖素免疫活性内分泌细胞在草鱼整个肠道中均呈阳性反应;在鲤、青鱼前肠中仅有少量阳性反应;在翘嘴红鲌肠道中未见阳性反应。胃蛋白酶原(Pepsinogen)、凝乳酶(Prochymosin)和神经特异烯醇酶(Neuron specific enolase)3种抗血清在4种鱼的肠道中均未发现阳性反应.本文重点描述草鱼高血糖素免疫活性内分泌细胞在肠道各段的分布,密度及其形态学特征,还就其可能的生理功能与草食性哺乳动物胃肠道中该类内分泌细胞进行比较和讨论。展开更多
Background:Neurogenin-3(NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine.The NEUROG3 gene(NEUROG3) is therefore a candidate for the cause...Background:Neurogenin-3(NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine.The NEUROG3 gene(NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells.Methods:We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3.We then tested the ability of the observed mutations to alter NEUROG3 function,using in vitro and in vivo assays.Results:The patients had few intestinal enteroendocrine cells positive for chromogranin A,but they had normal numbers of Paneth’s,goblet,and absorptive cells.We identified two homozygous mutations in NEUROG3,both of which rendered the NEUROG3 protein unable to activate NEUROD1,a downstream target of NEUROG3,and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter.The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression.Conclusions:A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3.展开更多
文摘We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologically and functionally. Because normal enterocytes were present, we hypothesized that this patient had a developmental block in the differentiation of a common stem cell precursor for Paneth, goblet, and neuroendocrine lineages. By using antibodies to protein markers of each cell line, including some that are expressed early in the differentiation process, we aimed to study lineage development in this patient. From our data, we surmise that there may be a two-step process in lineage commitment. The stem cell may commit to an absorptive cell or a granule-containing cell. The daughter cell that is committed to the granule lineage then further commits to a goblet, enteroendocrine, or Paneth cell lineage.
文摘应用过氧化物酶抗过氧化物酶(PAP)免疫组织化学技术,用4种哺乳动物中培育出的抗血清对草鱼、青鱼、鲤和翘嘴红鲌4种鲤科鱼的肠内分泌细胞进行免疫、组织化学的鉴别和定位.证实了高血糖素免疫活性内分泌细胞在草鱼整个肠道中均呈阳性反应;在鲤、青鱼前肠中仅有少量阳性反应;在翘嘴红鲌肠道中未见阳性反应。胃蛋白酶原(Pepsinogen)、凝乳酶(Prochymosin)和神经特异烯醇酶(Neuron specific enolase)3种抗血清在4种鱼的肠道中均未发现阳性反应.本文重点描述草鱼高血糖素免疫活性内分泌细胞在肠道各段的分布,密度及其形态学特征,还就其可能的生理功能与草食性哺乳动物胃肠道中该类内分泌细胞进行比较和讨论。
文摘Background:Neurogenin-3(NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine.The NEUROG3 gene(NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells.Methods:We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3.We then tested the ability of the observed mutations to alter NEUROG3 function,using in vitro and in vivo assays.Results:The patients had few intestinal enteroendocrine cells positive for chromogranin A,but they had normal numbers of Paneth’s,goblet,and absorptive cells.We identified two homozygous mutations in NEUROG3,both of which rendered the NEUROG3 protein unable to activate NEUROD1,a downstream target of NEUROG3,and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter.The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression.Conclusions:A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3.
