克鲁佩尔样因子5激活的肠干细胞,并促进粘膜在损伤后的修复
Lingzi Yu1, Sichao Qi1,2, Guozhen Wei3
1Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, P.R. China.
Cell cycle (Georgetown, Tex.)
|November 11, 2023
概括
克鲁佩尔样因子5 (KLF5) 通过STAT5A直接激活储备肠干细胞 (rISCs),间接通过STAT5A激活活跃ISCs (aISCs),在受伤后启动粘膜修复.
科学领域:
- 动物科学动物科学
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
背景情况:
- 肠干细胞 (ISC) 的活性对于粘膜的更新和修复至关重要.
- 储备ISCs (rISCs) 的激活对于启动受伤后的修复至关重要,但的机制尚不清楚.
研究的目的:
- 为了阐明在脂聚糖化物 (LPS) 挑战后中rISC激活的调节机制.
- 研究KLF5和STAT5A在ISC激活和粘膜修复中的作用.
主要方法:
- 和有机体模型中的脂聚糖 (LPS) 挑战.
- 通过mRNA和蛋白质水平分析ISC标记物 (Lgr5,Hopx) 和细胞周期标记物 (Ccnd1,Cdk2).
- 使用KLF5 (ML264) 和STAT5A (AC-4-130) 抑制剂的抑制研究.
- 双路西法酶记者测试以确认促进体结合和激活.
主要成果:
- LPS挑战诱导了线粒体功能障碍和降低了上皮质分泌,但加速了粘膜的更新.
- 早期的损伤显示活跃ISCs减少 (Lgr5) 和增加储备ISCs (Hopx).
- KLF5被上调; KLF5抑制降低了Stat5a和Hopx,而STAT5A抑制抑制了Lgr5.5.
- KLF5通过STAT5A直接激活rISCs (Hopx促进器),并通过STAT5A间接激活aISCs (Lgr5促进器).
结论:
- KLF5上调启动粘膜修复,通过激活储备和活跃的肠干细胞.
- KLF5直接激活rISC,并通过STAT5A通路间接激活aISC.
- 这项研究揭示了肠粘膜修复的新型调节机制.
相关概念视频
01:23Renewal of Intestinal Stem Cells
2.6K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.6K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
01:33Adult Stem Cells
29.9K
Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
29.9K
01:14Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K
01:26Stem Cell Niche
5.1K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
5.1K