Heterogeneity of SOX9 and HNF1β in Pancreatic Ducts Is Dynamic

被引:29
作者
Rezanejad, Habib [1 ]
Ouziel-Yahalom, Limor [1 ]
Keyzer, Charlotte A. [1 ]
Sullivan, Brooke A. [1 ]
Hollister-Lock, Jennifer [1 ]
Li, Wan-Chun [1 ]
Guo, Lili [1 ]
Deng, Shaopeng [2 ]
Lei, Ji [2 ]
Markmann, James [2 ]
Bonner-Weir, Susan [1 ]
机构
[1] Harvard Med Sch, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA
[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA
关键词
ADULT-MOUSE PANCREAS; IN-VITRO EXPANSION; BETA-CELLS; PROGENITOR CELLS; STEM-CELLS; REGENERATION; DIFFERENTIATION; IDENTIFICATION; EXPRESSION; ENDOCRINE;
D O I
10.1016/j.stemcr.2018.01.028
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with pancreatic duct-specific Cre expression have given conflicting results. Using immunofluorescence and flow cytometry, we show heterogeneous expression of both HNF1 beta and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after induced replication. Purified pancreatic duct cells formed organoid structures in 3D culture, and heterogeneity of expression of Hnf1 beta and Sox9 was maintained even after passaging. Using antibodies against a second cell surface molecule CD51 (human) or CD24 (mouse), we could isolate living subpopulations of duct cells enriched for high or low expression of HNF1 beta and SOX9. Only the CD24(high) (Hnf beta(high)/Sox9(high)) subpopulation was able to form organoids.
引用
收藏
页码:725 / 738
页数:14
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