Hnf4激活模仿细胞增强剂,在胆小板内复制肠道和肝脏的发育
Daniel A Michelson1, Chong Zuo1, Michael Verzi2,3
1Department of Immunology, Harvard Medical School, Boston, MA, USA.
The Journal of experimental medicine
|July 3, 2023
概括
肝细胞核因子4 (Hnf4) 转录因子控制了胸腺中的模仿细胞,使T细胞对自身抗原产生耐受性. 它们的丧失影响了基因调节,细胞命运和肠道中的免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 骨髓胸膜上皮细胞 (mTECs) 通过向T细胞呈现自身抗原来建立自我耐受性至关重要.
- 在mTECs中的模拟细胞表达通常存在于体外组织 (如肠道和肝脏) 的转录.
- 控制这些模仿细胞的功能和身份的分子机制尚未完全理解.
研究的目的:
- 研究转录因子Hnf4α和Hnf4γ在肝模仿细胞生物学中的作用.
- 阐明Hnf4因子如何调节mTECs中的基因表达,染色质可访问性和细胞命运.
- 探索Hnf4功能对胸膜和外周免疫反应的更广泛影响.
主要方法:
- 使用单细胞RNA测序来分析Hnf4删除对mTEC群体的影响.
- 染色体免疫沉和基因表达分析被用来评估增强剂活性和基因调节.
- 在胸膜上皮细胞 (TECs) 中进行了基因操纵 (删除Hnf4α和Hnf4γ).
主要成果:
- 在TEC中删除Hnf4α和Hnf4γ导致了肠-肝 mTEC的切除,并减少了肠和肝相关基因的表达,其中Hnf4γ是主要的贡献者.
- 失去Hnf4会影响增强剂激活和mTEC中CTCF的再分配,但不会影响Polycomb介导的抑制.
- 单细胞RNA测序揭示了Hnf4损失对模仿细胞状态,命运和积累的明显影响,并揭示了Hnf4γ在肠道微细胞和IgA反应中的作用.
结论:
- Hnf4转录因子是肠肝mTECs的重要调节者,控制它们的身份和基因表达程序.
- Hnf4控制mTEC中的增强剂活性和染色质组织,有助于T细胞的自我耐受性.
- 这项研究揭示了Hnf4在外周免疫力中的新型作用,特别是肠道微细胞和IgA生产,突出了保存的基因调节机制.
相关概念视频
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
01:16TGF - β Signaling Pathway
7.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
02:33Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.3K
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.
2.3K
01:29Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K