Yoshida Tetsu, Shiraki Nobuaki, Baba Hideo, Goto Mizuki, Fujiwara Sakuhei, Kume Kazuhiko, Kume Shoen
Division of Stem Cell Biology, Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Japan.
Genes Cells. 2008 Jul;13(7):667-78. doi: 10.1111/j.1365-2443.2008.01196.x. Epub 2008 May 21.
Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the plakin genes are known to function in interconnecting cytoskeletal filaments and anchoring them at plasma membrane-associated adhesive junction. Here we analyzed the expression patterns of Eppk1 in the developing and adult pancreas in the mice. In the embryonic pancreas, Eppk1+/Pdx1+ and Eppk1+/Sox9+ pancreatic progenitor cells were observed in early pancreatic epithelium. Since Pdx1 expression overlapped with that of Sox9 at this stage, these multipotent progenitor cells are Eppk1+/Pdx1+/Sox9+ cells. Then Eppk1 expression becomes confined to Ngn3+ or Sox9+ endocrine progenitor cells, and p48+ exocrine progenitor cells, and then restricted to the duct cells and a cells at birth. In the adult pancreas, Eppk1 is expressed in centroacinar cells (CACs) and in duct cells. Eppk1 is observed in pancreatic intraepithelial neoplasia (PanIN), previously identified as pancreatic ductal adenocarcinoma (PDAC) precursor lesions. In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. Furthermore, in the partial pancreatectomy (Px) regeneration model using mice, Eppk1 is expressed in "ducts in foci", a tubular structure transiently induced. These results suggest that Eppk1 serves as a useful marker for detecting pancreatic progenitor cells in developing and regenerating pancreas.
表皮 plak 蛋白 1(Eppk1)是一种 plak 家族基因,尽管已知 plak 基因在连接细胞骨架丝并将其锚定在质膜相关黏附连接处发挥作用,但其功能在很大程度上仍不清楚。在这里,我们分析了 Eppk1 在小鼠发育中和成年胰腺中的表达模式。在胚胎胰腺中,在早期胰腺上皮中观察到 Eppk1+/Pdx1+和 Eppk1+/Sox9+胰腺祖细胞。由于在此阶段 Pdx1 的表达与 Sox9 的表达重叠,这些多能祖细胞是 Eppk1+/Pdx1+/Sox9+细胞。然后 Eppk1 的表达局限于 Ngn3+或 Sox9+内分泌祖细胞以及 p48+外分泌祖细胞,随后在出生时局限于导管细胞和α细胞。在成年胰腺中,Eppk1 在中央腺泡细胞(CACs)和导管细胞中表达。在胰腺上皮内瘤变(PanIN)中观察到 Eppk1,PanIN 先前被确定为胰腺导管腺癌(PDAC)的前体病变。此外,在雨蛙肽诱导的急性胰腺炎(一种腺泡细胞再生模型)中,Eppk1 阳性细胞会扩张。此外,在使用小鼠的部分胰腺切除术(Px)再生模型中,Eppk1 在“灶性导管”(一种短暂诱导的管状结构)中表达。这些结果表明,Eppk1 可作为检测发育中和再生胰腺中胰腺祖细胞的有用标志物。