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转录因子PRDM16维持肠上皮稳态
作者:小柯机器人 发布时间:2019/9/29 14:24:56

美国宾夕法尼亚大学Patrick Seale和Rachel R. Stine等研究人员合作发现,转录因子PRDM16通过调控区域特定的代谢来维持肠道上皮的稳态。该项研究成果2019年9月26日在线发表于《细胞—干细胞》。

研究人员将转录因子PRDM16定义为肠道代谢和上皮更新的区域特定调节者。PRDM16在上消化道中选择性表达,并在隐窝祖细胞中富集。小鼠中急性Prdm16缺失引发祖细胞凋亡,导致上皮分化减少和严重的肠萎缩。基因组和代谢分析表明PRDM16转录控制隐窝中的脂肪酸氧化(FAO)。由PRDM16驱动的FAO程序表达在小肠上部最高,而在远端则下降。因此,Prdm16的缺失或对FAO的抑制选择性地损害了上消化道小肠的形成和维持,并且通过醋酸盐治疗可以挽救这些作用。这些数据共同表明,区域特定的代谢程序可调节肠道维持。

据悉,代谢途径动态调节组织的发育和维持。然而,控制干细胞或祖细胞对其局部微环境代谢适应的机制了解甚少。

附:英文原文

Title: PRDM16 Maintains Homeostasis of the Intestinal Epithelium by Controlling Region-Specific Metabolism

Author: Rachel R. Stine, Alexander P. Sakers, Tara TeSlaa, Megan Kissig, Zachary E. Stine, Chan Wook Kwon, Lan Cheng, Hee-Woong Lim, Klaus H. Kaestner, Joshua D. Rabinowitz, Patrick Seale

Issue&Volume: 26 September 2019

Abstract: 

Metabolic pathways dynamically regulate tissue development and maintenance. However, the mechanisms that govern the metabolic adaptation of stem or progenitor cells to their local niche are poorly understood. Here, we define the transcription factor PRDM16 as a region-specific regulator of intestinal metabolism and epithelial renewal. PRDM16 is selectively expressed in the upper intestine, with enrichment in crypt-resident progenitor cells. Acute Prdm16 deletion in mice triggered progenitor apoptosis, leading to diminished epithelial differentiation and severe intestinal atrophy. Genomic and metabolic analyses showed that PRDM16 transcriptionally controls fatty acid oxidation (FAO) in crypts. Expression of this PRDM16-driven FAO program was highest in the upper small intestine and declined distally. Accordingly, deletion of Prdm16 or inhibition of FAO selectively impaired the development and maintenance of upper intestinal enteroids, and these effects were rescued by acetate treatment. Collectively, these data reveal that regionally specified metabolic programs regulate intestinal maintenance.

DOI: 10.1016/j.stem.2019.08.017

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30384-4

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx