Single pancreatic beta cells co-express multiple islet hormone genes in mice.
Single pancreatic beta cells co-express multiple islet hormone genes in mice.
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单胰腺β细胞在小鼠中共表达多种胰岛激素基因。
DOI：
10.1007/s00125-009-1570-x
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发表时间：
2010-01
期刊：
影响因子：
8.2
通讯作者：
Weir, G. C.
中科院分区：
文献类型：
--
作者：
Katsuta, H.;Akashi, T.;Katsuta, R.;Nagaya, M.;Kim, D.;Arinobu, Y.;Hara, M.;Bonner-Weir, S.;Sharma, A. J.;Akashi, K.;Weir, G. C.
人们普遍认为，胰岛细胞产生的胰岛素、胰升糖素、生长抑素和胰多肽分别是β细胞、α细胞、β细胞和胰多肽细胞所特有的。我们检查了β细胞是否表达其他编码胰岛激素的基因。对携带小鼠胰岛素I启动子(MIP-GFP)驱动的绿色荧光蛋白(GFP)的转基因小鼠的单个β细胞进行巢式RT-PCR。只有55%的成年β细胞只表达胰岛素基因，而其他细胞表达两种或两种以上的胰岛激素基因；4%的细胞表达所有四种激素基因。在胚胎和新生儿细胞中，60%~80%的GFP+细胞共表达胰多肽和胰岛素基因，而成年细胞中这一比例为29%。为了弄清细胞命运，我们用大鼠胰岛素II启动子-cre小鼠与报告小鼠GT(ROSA)26Sor-loxP侧翼Stop-cassette-GFP杂交进行了谱系追踪。所有GFP+细胞都表达胰岛素I和II基因，并显示出与MIP-GFP小鼠相似的共表达异质性。尽管我们报告了在相当大比例的β细胞中表达其他激素基因，但我们的谱系追踪结果表明，在诱导InsII(也称为Ins2)表达后，β细胞前体细胞不会重新分化为非β细胞。这项研究表明，多种激素基因在成年小鼠的β细胞以及胚胎和新生儿中共同表达。这一发现可能：(1)代表来自β细胞前体的残留表达；(2)来自不同发育途径的β细胞；或(3)代表这些细胞的分化潜力。这可能与功能异质性有关。基因表达的这种异质性可能提供了一种手段来表征在贝塔细胞中看到的功能、细胞和发育的异质性。本文的在线版本(doi：10.1007/s00125-009-1570-x)包含补充材料，可供授权用户使用。
It is widely accepted that production of insulin, glucagon, somatostatin and pancreatic polypeptide in islet cells is specific to beta, alpha, delta and pancreatic polypeptide cells, respectively. We examined whether beta cells express other genes encoding islet hormones. Nested RT-PCR was performed on single beta cells of transgenic mice with green fluorescent protein (GFP) driven by mouse insulin I promoter (MIP-GFP). Only 55% of adult beta cells expressed the insulin gene alone, while others expressed two or more islet hormone genes; 4% expressed all four hormone genes. In embryonic and neonatal cells, 60% to 80% of GFP+ cells co-expressed pancreatic polypeptide and insulin genes in contrast to 29% in adult. To clarify cell fate, we conducted lineage tracing using rat insulin II promoter-cre mice crossed with reporter mice Gt(ROSA)26Sor-loxP-flanked STOP-cassette-GFP. All GFP+ cells expressed insulin I and II genes, and showed similar heterogeneity of co-expression to that seen in MIP-GFP mice. Although we report expression of other hormone genes in a significant proportion of beta cells, our lineage tracing results demonstrate that after inducing InsII (also known as Ins2) expression, beta cell progenitors do not redifferentiate to non-beta cells. This study shows co-expression of multiple hormone genes in beta cells of adult mice as well as in embryos and neonates. This finding could: (1) represent residual expression from beta cell precursors; (2) result from alternative developmental pathways for beta cells; or (3) denote the differentiation potential of these cells. It may be linked to functional heterogeneity. This heterogeneity in gene expression may provide a means to characterise the functional, cellular and developmental heterogeneity seen in beta cells. The online version of this article (doi:10.1007/s00125-009-1570-x) contains supplementary material, which is available to authorised users.
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影响因子：
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作者：
DEVASKAR, SU;SINGH, BS;GIDDINGS, SJ
通讯作者：
GIDDINGS, SJ
影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1152/ajpendo.00321.2002
发表时间：
2003-01-01
影响因子：
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通讯作者：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.97.14.7999
发表时间：
2000-07-05
影响因子：
11.1
作者：
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通讯作者：
O'Neil, JJ