轉錄因子PRDM16維持腸上皮穩態
作者：
小柯機器人發布時間：2019/9/29 14:24:56
美國賓夕法尼亞大學Patrick Seale和Rachel R. Stine等研究人員合作發現，轉錄因子PRDM16通過調控區域特定的代謝來維持腸道上皮的穩態。該項研究成果2019年9月26日在線發表於《細胞—幹細胞》。
研究人員將轉錄因子PRDM16定義為腸道代謝和上皮更新的區域特定調節者。PRDM16在上消化道中選擇性表達，並在隱窩祖細胞中富集。小鼠中急性Prdm16缺失引發祖細胞凋亡，導致上皮分化減少和嚴重的腸萎縮。基因組和代謝分析表明PRDM16轉錄控制隱窩中的脂肪酸氧化（FAO）。由PRDM16驅動的FAO程序表達在小腸上部最高，而在遠端則下降。因此，Prdm16的缺失或對FAO的抑制選擇性地損害了上消化道小腸的形成和維持，並且通過醋酸鹽治療可以挽救這些作用。這些數據共同表明，區域特定的代謝程序可調節腸道維持。
據悉，代謝途徑動態調節組織的發育和維持。然而，控制幹細胞或祖細胞對其局部微環境代謝適應的機制了解甚少。
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