ALDH1B1 is a potential stem/progenitor marker for multiple pancreas progenitor pools
ALDH1B1 is a potential stem/progenitor marker for multiple pancreas progenitor pools
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DOI：
10.1016/j.ydbio.2012.10.030
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发表时间：
2013-02-01
影响因子：
2.7
通讯作者：
Gavalas, Anthony
中科院分区：
文献类型：
--
作者：
Ioannou, Marilia;Serafimidis, Ioannis;Gavalas, Anthony
乙醛脱氢酶（ALDH）基因越来越多地与干/祖细胞的状态，但其在维持多能性的作用仍然不确定。在使用ES衍生的胰腺祖细胞对下游Ngn 3靶基因进行的筛选中，我们鉴定了编码线粒体酶的Aldh 1b 1作为响应Ngn 3表达而强烈上调的基因之一。我们发现，无论是通过原位杂交和免疫荧光使用的特异性抗体，ALDH 1B 1是专门表达在新兴的胰腺芽的早期胚胎（9.5 dpc）在Pdx 1依赖的方式。在第二次跃迁的时候。ALDH 1B 1的表达被限制在尖端三能祖细胞的分支上皮和在一个子集的干上皮。在后者中的表达是Ngn 3依赖的。随后，ALDH 1B 1的表达只持续在尖端细胞，成为限制外分泌谱系，并迅速下降，因为这些细胞成熟。在成人胰腺中，我们发现了罕见的ALDH 1B 1（+）细胞，在雨蛙肽或链脲佐菌素的范例中胰腺损伤后变得丰富。阻断胰腺胚胎外植体中的ALDH催化活性导致外植体尺寸减小和分化加速，这首次表明ALDH活性在发育中的胰腺中对于祖细胞库的维持和扩增可能是必需的。(c)2012 Elsevier Inc. All rights reserved.
Aldehyde dehydrogenase (ALDH) genes are increasingly associated with stem/progenitor cell status but their role in the maintenance of pluripotency remains uncertain. In a screen conducted for downstream Ngn3 target genes using ES derived pancreas progenitors we identified Aldh1b1, encoding a mitochondrial enzyme, as one of the genes strongly up regulated in response to Ngn3 expression. We found both by in situ hybridization and immunofluorescence using a specific antibody that ALDH1B1 is exclusively expressed in the emerging pancreatic buds of the early embryo (9.5 dpc) in a Pdx1 dependent manner. Around the time of secondary transition. ALDH1B1 expression was restricted in the tip tripotent progenitors of the branching epithelium and in a subset of the trunk epithelium. Expression in the latter was Ngn3 dependent. Subsequently, ALDH1B1 expression persisted only in the tip cells that become restricted to the exocrine lineage and declined rapidly as these cells mature. In the adult pancreas we identified rare ALDH1B1(+) cells that become abundant following pancreas injury in either the caerulein or streptozotocin paradigms. Blocking ALDH catalytic activity in pancreas embryonic explants resulted in reduced size of the explants and accelerated differentiation suggesting for the first time that ALDH activity may be necessary in the developing pancreas for the maintenance and expansion of progenitor pools. (c) 2012 Elsevier Inc. All rights reserved.