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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Isolation and characterization of centroacinar/ terminal ductal progenitor cells in adult mouse pancreas
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Isolation and characterization of centroacinar/ terminal ductal progenitor cells in adult mouse pancreas

机译：成年小鼠胰腺中央棘突/末端导管祖细胞的分离和鉴定

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摘要

The question of whether dedicated progenitor cells exist in adult vertebrate pancreas remains controversial. Centroacinar cells and terminal duct (CA/TD) cells lie at the junction between peripheral acinar cells and the adjacent ductal epithelium, and are frequently included among cell types proposed as candidate pancreatic progenitors. However these cells have not previously been isolated in a manner that allows formal assessment of their progenitor capacities. We have found that a subset of adult CA/TD cells are characterized by high levels of ALDH1 enzymatic activity, related to high-level expression of both Aldh1a1 and Aldh1a7. This allows their isolation by FACS using a fluorogenic ALDH1 substrate. FACS-isolated CA/TD cells are relatively depleted of transcripts associated with differentiated pancreatic cell types. In contrast, they are markedly enriched for transcripts encoding Sca 7, Sdf1, c-Met, Nestin. and Sox9, markers previously associated with progenitor populations in embryonic pancreas and other tissues. FACS-sorted CA/TD cells are uniquely able to form self-renewing "pancreatospheres" in suspension culture, even when plated at clonal density. These spheres display a capacity for spontaneous endocrine and exocrine differentiation, as well as glucose-responsive insulin secretion. In addition, when injected into cultured embryonic dorsal pancreatic buds, these adult cells display a unique capacity to contribute to both the embryonic endocrine and exocrine lineages. Finally, these cells demonstrate dramatic expansion in the setting of chronic epithelial injury. These findings suggest that CA/TD cells are indeed capable of progenitor function and may contribute to the maintenance of tissue homeostasis in adult mouse pancreas.
机译：在成年脊椎动物胰腺中是否存在专用祖细胞的问题仍存在争议。中心腺泡细胞和末梢导管（CA / TD）细胞位于周围腺泡细胞和相邻的导管上皮之间的交界处，并且经常被包括在提议作为候选胰腺祖细胞的细胞类型中。但是，这些细胞以前尚未以允许对其祖细胞能力进行正式评估的方式进行分离。我们已经发现，成年CA / TD细胞的一个子集具有高水平的ALDH1酶促活性，与Aldh1a1和Aldh1a7的高水平表达有关。这允许使用荧光ALDH1底物通过FACS分离它们。 FACS分离的CA / TD细胞相对缺乏与分化的胰腺细胞类型相关的转录本。相反，它们显着丰富了编码Sca 7，Sdf1，c-Met和Nestin的转录本。 Sox9和以前与胚胎胰腺和其他组织中的祖细胞群相关的标记物。 FACS分选的CA / TD细胞即使在克隆密度下铺板，也能在悬浮培养中独特地形成自我更新的“胰腺球”。这些球体具有自发性内分泌和外分泌分化以及葡萄糖反应性胰岛素分泌的能力。此外，当将它们注入培养的胚胎背胰胰芽中时，这些成年细胞显示出独特的能力，可同时参与胚胎内分泌和外分泌谱系。最后，这些细胞在慢性上皮损伤的情况下显示出惊人的扩增。这些发现表明，CA / TD细胞确实具有祖细胞功能，并且可能有助于维持成年小鼠胰腺的组织稳态。

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  • 作者

    Meritxell Rovira; Sherri-Gae Scott; Andrew S. Liss; Jan Jensen; Sarah P. Thayer; Steven D. Leach;

  • 作者单位

    Department of Surgery and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205;

    Department of Surgery and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205;

    Department of Surgery, Massachusetts General Hospital and Harvard University, Boston, MA 02114;

    Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195;

    Department of Surgery, Massachusetts General Hospital and Harvard University, Boston, MA 02114;

    Department of Surgery and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    ALDH1; CD133; pancreatic; pancreatosphere; stem cell;

    机译：ALDH1;CD133;胰;胰圈干细胞;

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