RUNX2在炎症的肠上皮细胞中促进了表观遗传WNT信号传递
Rodolfo I Cabrera-Silva1, Zachary S Wilson1, Jael Miranda1
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
bioRxiv : the preprint server for biology
|December 3, 2025
概括
性结肠炎 (UC) 涉及肠道愈合受损. 这项研究揭示了UC上皮细胞中RUNX2驱动的WNT信号缺陷,影响自我更新和成熟.
科学领域:
- 胃肠道学和分子生物学
- 炎症性肠道疾病研究研究
- 皮质生物学 皮质生物学
背景情况:
- 性结肠炎 (UC) 标志着慢性炎症,上皮损伤和伤口愈合不良.
- WNT/β-catenin通路失调与UC有关,但潜在的机制尚不清楚.
- 了解内在上皮缺陷对于UC的发病过程至关重要.
研究的目的:
- 通过使用多组学来研究UC的表皮内在变化.
- 确定驱动UC中WNT/β-catenin失调的分子机制.
- 探索RUNX2在UC上皮细胞功能中的作用.
主要方法:
- 单核RNA-seq (snRNA-seq) 和ATAC-seq (snATAC-seq) 在来自健康和UC捐赠者的人类结肠体上.
- 在3D (密码基础) 和2D (光上皮质) 模型中培养结肠.
- 使用CADD522.2.使用RUNX2的药理抑制.
主要成果:
- 一个独特的UC关联细胞群体显示CTNNB1升高和APC表达减少.
- 染色体分析显示,在这个群体中,RUNX2基因丰富.
- 在UC结肠体上,OLFM4 (3D) 和VIL1 (2D) 的表达减少,表明更新和成熟受损.
- 抑制RUNX2恢复了VIL1的表达和结点β-catenin的局部化.
结论:
- UC在上皮膜更新中表现出一种内在的缺陷.
- 取决于RUNX2的WNT失调有助于UC的发病.
- RUNX2被确定为表皮干细胞功能和炎症结肠中WNT信号的关键调节者.
相关概念视频
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
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.
2.6K
02:54Canonical Wnt Signaling Pathway
10.3K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.3K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
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...
2.4K
01:23Renewal of Intestinal Stem Cells
3.1K
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...
3.1K
01:41Non-Canonical Wnt Signaling Pathways
8.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
03:17Inheritance of Chromatin Structures
7.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.2K