染色体重塑因子Mll1对于产后神经干细胞的神经发生是必不可少的
Daniel A Lim1, Yin-Cheng Huang, Tomek Swigut
1Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Street M779, San Francisco, California 94143, USA. limd@neurosurg.ucsf.edu
Nature
|February 13, 2009
概括
混合系白血病1 (Mll1) 对于成年人的神经发生是必不可少的. Mll1解决了沉默的基因位置,使出生后大脑中的神经元分化成为可能.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 成人神经发生依赖于表观遗传机制,其中Trithorax组 (trxG) 和Polycomb组 (PcG) 基因调节色素.
- 虽然已知PcG成员Bmi1对神经干细胞自我更新至关重要,但trxG基因在这一过程中的作用尚未被探索.
研究的目的:
- 研究trxG基因Mll1 (混合系白血病1) 在产后神经发生的作用.
- 阐明Mll1影响子室下区域神经元分化的分子机制.
主要方法:
- 对Mll1缺乏的小鼠进行分析,以评估出生后大脑中的神经发生.
- 在神经干细胞中的基因表达分析 (Mash1,Olig2,Dlx2).
- 染色体免疫沉用于识别MLL标.
- 在基因位置的基因修饰分析 (H3K4me3,H3K27me3).
主要成果:
- 缺少Mll1的神经干细胞表现出神经区分受损,但神经质区分正常.
- 关键的神经发生调节器Dlx2的表达在Mll1缺乏细胞中被废除.
- Dlx2是直接的MLL标,其位点在Mll1缺陷细胞中显示双价组素标记 (H3K4me3和H3K27me3),防止激活.
结论:
- 通过激活Dlx2.2等关键基因的表达,Mll1对于产后神经发生是不可或缺的.
- Mll1通过在关键发育位点解决双价色色素标记来起作用,从而促进神经元分化.
- 这些发现突出了一个新的表观遗传机制调节成人神经发生.
相关概念视频
01:14Maintenance of the ES Cell State
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...
01:29Somatic to iPS Cell Reprogramming
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 for this...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
01:24Methods of Nuclear Reprogramming
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
01:15Neurogenesis and Regeneration of Nervous Tissue
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...