寄生虫诱导肠道干细胞中的胎儿类逆转
Ysbrand M Nusse1,2, Adam K Savage3, Pauline Marangoni2
1Biomedical Sciences Graduate Program, University of California, San Francisco, CA, USA.
Nature
|June 29, 2018
概括
成人肠道干细胞可以恢复到类似胎儿的状态来修复受损组织. 这项研究揭示了肠道干细胞 (ISC) 如何在受伤后重建肠道屏障, 重新调整发育途径.
科学领域:
- 胃肠病学
- 干细胞生物学
- 免疫学
背景情况:
- 成人干细胞维持上皮组织,但它们在受伤后的修复机制尚未完全理解.
- 甲状腺多胞体感染破坏了十二指肠粘膜屏障,为研究上皮质修复创造了一个模型.
- 在受伤诱导的上皮细胞增殖过程中,肠道干细胞标记物Lgr5通常会下调.
研究的目的:
- 研究成年肠道干细胞如何在粘膜屏障破坏后启动修复.
- 了解干扰素- (IFN-γ) 在上皮损伤反应中的作用.
- 确定成人肠道组织是否能够重新激活发育程序以进行修复.
主要方法:
- 检查了感染Heligmosomoides polygyrus的小鼠的上皮反应.
- 在粒瘤相关密码中评估肠道干细胞标记物的表达 (例如,Lgr5).
- 分析了转录程序,包括Sca-1和干扰素- (IFN-γ) 信号.
- 在体外培养与颗粒瘤相关的密码细胞以观察球形形成和转录变化.
- 对全身免疫激活,肠道辐射和Lgr5+干细胞切除的反应进行比较.
主要成果:
- 尽管有扩散,但与颗粒瘤相关的密码缺乏Lgr5表达.
- 一个依赖于IFN-γ的转录程序,包括Sca-1,在Lgr5-阴性隐形上皮层中被激活.
- 在颗粒瘤中存在产生IFN-γ的免疫细胞.
- 在全身免疫激活,照射或干细胞切除后观察到类似的上皮反应.
- 在试验室中,与颗粒瘤相关的密码细胞形成了类似胎儿的球体,并表现出类似胎儿的转录程序.
结论:
- 成人肠道干细胞可以重新编程并激活类似胎儿发育的程序来修复受损的组织.
- 干扰素的信号传递在介导上皮质对损伤的反应中起着至关重要的作用.
- 重新利用发育途径是肠道密室重建和受伤后功能恢复的基本机制.
相关概念视频
01:26Stem Cell Niche
6.4K
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...
6.4K
01:06Multipotency and Niche of Bulge Stem Cell
4.2K
A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
4.2K
01:13Induced Pluripotent Stem Cells
28.1K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.1K
01:06Induced Pluripotent Stem Cells
5.6K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
5.6K
02:02Ecological Niches
26.7K
All organisms have a position within an ecosystem. The complete set of living and nonliving factors—including food resources, climate, and terrain—that define the position of a given organism are collectively referred to as the organism’s ecological niche.
26.7K
01:23Renewal of Intestinal Stem Cells
3.3K
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...
3.3K