Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation.
Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation.
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DOI：
10.1016/j.jcmgh.2014.12.004
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发表时间：
2015-03
影响因子：
7.2
通讯作者：
Jensen J
中科院分区：
文献类型：
--
作者：
Qu X;Nyeng P;Xiao F;Dorantes J;Jensen J
区隔性胰腺腺泡/中央腺泡单位的遗传特征尚不清楚。生长因子独立-1 （Growth factor independence-1, Gfi1）是一种锌指转录抑制因子，调节造血干细胞的维持、t细胞前分化、粒细胞的形成、内耳毛细胞和肠道分泌细胞类型的发育。由于GFI1/ GFI1在人和啮齿动物胰腺中表达，我们表征了GFI1在小鼠胰腺发育中的潜在功能。对Gfi1基因敲除小鼠进行组织学和分子水平的分析，包括qRT-PCR、原位杂交、免疫组织化学和电镜。Gfi1的缺失影响了胰腺腺泡/中央腺泡单位的形成和结构。与野生型小鼠相比，Gfi1- / -小鼠胰腺的组织学和超微结构分析显示，Gfi1- / -小鼠胰腺腺泡细胞和中央腺泡细胞（CACs）水平存在特异性缺陷。胰腺内分泌分化、胰岛结构和功能未受影响。在小鼠Gfi1−/−胰腺的继发性转移（E13.5-E14.5）期间，器官结构域模式和导管细胞的形成正常发生。然而，在妊娠后期（E18.5）， Gfi1−/−小鼠中CACs细胞标记物的表达显著降低，这一点得到了腺泡/中央腺泡单位的电镜成像的证实。CACs的减少与外分泌器官缺陷有关。出生后，Gfi1缺乏导致严重的胰腺腺泡发育不良，包括肉芽缺失、自溶空泡形成、增殖和凋亡反应。Gfi1在调节胰腺cac的发育和胰腺腺泡细胞的功能中起重要作用。
The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. Gfi1 knockout mice were analyzed at histological and molecular levels, including qRT-PCR, in situ hybridization, immunohistochemistry, and electron microscopy. Loss of Gfi1 impacted formation and structure of the pancreatic acinar/centroacinar unit. Histologic and ultrastructural analysis of Gfi1-null pancreas revealed specific defects at the level of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1−/− mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine secondary transition (E13.5–E14.5) in the Gfi1−/− pancreas. However, at later gestational time points (E18.5), expression of cellular markers for CACs was substantially reduced in Gfi1−/− mice, corroborated by electron microscopy imaging of the acinar/centroacinar unit. The reduction in CACs was correlated with an exocrine organ defect. Postnatally, Gfi1 deficiency resulted in severe pancreatic acinar dysplasia, including loss of granulation, autolytic vacuolation, and a proliferative and apoptotic response. Gfi1 plays an important role in regulating the development of pancreatic CACs and the function of pancreatic acinar cells.