来自杂志 Nature Cell Biology 的文献。
当前共找到 3 篇文献分享。
1.
孤舟蓑笠翁
(2025-10-17 20:12):
paper 【doi】10.1038/s41556-025-01769-9；【发表年份】2025年；【期刊】Nature Cell Biology；【标题】Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma。【内容总结】这项研究想搞清楚为什么压力会导致头发变白或黑色素瘤，发现关键在于黑色素干细胞（McSCs）在受到不同基因毒素时的命运选择。简单说，像辐射这样的压力会让McSCs进入“衰老分化”（同时衰老和分化），导致它们从毛囊中消失，头发就变白了，但这能防止黑色素瘤；而像DMBA（一种致癌物）或紫外线这样的压力会通过激活花生四烯酸代谢和毛囊干细胞产生的KIT配体（KITL），阻止McSCs衰老分化，促进它们自我更新和迁移到皮肤表层，从而增加黑色素瘤风险。研究方法上，他们用了小鼠模型进行体内命运追踪（比如用Dct-H2B-GFP或Dct-LacZ标记McSCs）、免疫组化分析、RNA测序（包括单细胞和批量RNA-seq）、流式细胞术分选细胞以及体外实验（如彗星试验测DNA损伤）。结果发现，辐射诱导的DNA双链断裂会激活p53-p21通路，使McSCs在激活后衰老分化并最终被清除（例如，5 Gy辐射导致McSCs数量显著减少），而致癌物处理能上调KITL表达（如DMBA使KITL表达增加），并通过激活下游信号（如NRAS或BRAF突变）绕过这一过程；此外，年龄增长会降低KITL等因子表达，促进头发变白，而KITL过表达能挽救辐射引起的白发。总之，McSCs的命运取决于压力类型：致癌压力促进自我更新和癌症，而细胞毒性压力导致衰老分化和白发，两者在干细胞水平上存在拮抗关系。
2.
孤舟蓑笠翁
(2025-09-03 21:40):
paper 【doi】10.1038/s41556-025-01751-5；【发表年份】2025年；【期刊】Nature Cell Biology；【标题】Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing。【内容总结】这篇论文研究了人类胚胎发育速度比其它物种慢的原因，通过全基因组CRISPR筛选发现表观遗传调控因子Menin和SUZ12是关键计时器。研究人员首先建立了PAX6::H2B-GFP报告系统监测神经分化速度，然后用全基因组CRISPR-Cas9敲除筛选找到27个候选基因，其中Menin和SUZ12缺失使神经分化显著加速。通过RNA测序、ATAC-seq和CUT&RUN等技术发现，这两个因子通过维持发育基因启动子区H3K4me3（激活标记）和H3K27me3（抑制标记）的平衡来控制分化速度：当Menin缺失时H3K4me3在bivalent启动子区增加，而SUZ12缺失则导致H3K27me3全局减少，都使发育基因更易被激活。这种加速效应不仅见于神经外胚层，在内胚层分化（GATA6/CXCR4表达提前）和心肌细胞分化（收缩提前）中也得到验证，说明这是跨胚层的通用计时机制。研究还发现小分子抑制剂VTP50469（靶向Menin-MLL）和Tazemetostat（靶向EZH2）能模拟基因敲除效果，为人工调控发育速度提供了工具。
Nature Cell Biology,
2025-9-2.
DOI: 10.1038/s41556-025-01751-5
Abstract:
Abstract Embryonic development follows a conserved sequence of events across species, yet the pace of development is highly variable and particularly slow in humans. Species-specific developmental timing is largely recapitulated …
>>>
Abstract Embryonic development follows a conserved sequence of events across species, yet the pace of development is highly variable and particularly slow in humans. Species-specific developmental timing is largely recapitulated in stem cell models, suggesting a cell-intrinsic clock. Here we use directed differentiation of human embryonic stem cells into neuroectoderm to perform a whole-genome CRISPR-Cas9 knockout screen and show that the epigenetic factors Menin and SUZ12 modulate the speed of PAX6 expression during neural differentiation. Genetic and pharmacological loss-of-function of Menin or SUZ12 accelerate cell fate acquisition by shifting the balance of H3K4me3 and H3K27me3 at bivalent promoters, thereby priming key developmental genes for faster activation upon differentiation. We further reveal a synergistic interaction of Menin and SUZ12 in modulating differentiation speed. The acceleration effects were observed in definitive endoderm, cardiomyocyte and neuronal differentiation paradigms, pointing to chromatin bivalency as a general driver of timing across germ layers and developmental stages.
<<<
翻译
3.
惊鸿
(2025-01-15 18:01):
#paper Mitotic lethality prevents inflammation
Pub Date : 2025-01-14
DOI : 10.1038/s41556-024-01529-1
现在一项研究发现，DNA 损伤后，通过同源重组修复 DNA 会驱动有丝分裂过程中非免疫原性细胞死亡。同源重组的缺失使细胞能够通过有丝分裂，但会驱动间期死亡和炎症。这表明免疫原性和非免疫原性细胞死亡模式之间存在二分法，具有生物医学潜力。
Nature Cell Biology,
2025-1.
DOI: 10.1038/s41556-024-01529-1
Abstract:
No abstract available.