Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis.
Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis.
复制标题
DOI：
10.1016/j.stemcr.2023.09.008
复制
发表时间：
2023-11-14
影响因子：
5.9
通讯作者：
Goldstein, Bradley J.
中科院分区：
文献类型：
--
作者：
Ko, Tiffany;Choi, Rhea;Issa, Khalil;Gupta, Rupali;Llinas, Edward;Morey, Lluis;Finlay, John B.;Goldstein, Bradley J.
成体神经发生发生在哺乳动物的嗅觉上皮细胞中，以维持对损伤敏感但对嗅觉至关重要的神经元群体。多能嗅觉基础干细胞被损伤激活，尽管调控谱系决定的机制尚不清楚。利用小鼠损伤模型，我们重点研究了多梳抑制复合体(PRCs)在嗅神经发生中的作用。PRC2在组织发育中具有广泛的作用，通过染色质修饰来协调转录程序。PRC2蛋白在嗅球基底细胞和新生神经元中表达。条件性PRC2缺失扰乱了损伤诱导的神经元产生，伴随着组蛋白修饰的改变和GBCS中谱系特异性转录因子的错误表达。在PrC2突变的GBCS中，Sox9的抑制伴随着Bowman腺体产量的增加，这定义了PrC2在调节腺与神经细胞命运方面的未知角色。我们的发现支持PRC2依赖的机制促进成人神经源性利基中感觉神经元分化的模型。在正常和损伤条件下，PRC2蛋白在嗅觉基底细胞中表达。H3K27me3标记了在嗅觉基底细胞中神经发生和分化活跃的基因。PRC2调节神经元和非神经元谱系之间的选择。发现PRC2是一种调节成人嗅觉上皮神经发生的机制。PrC2-突变的嗅觉基底细胞缺乏关键的H3K27me3标记，并抑制包括Sox9在内的非神经转录程序。谱系追踪的EDD缺陷的基底细胞产生更少的神经元和更多的非神经元细胞，包括鲍曼腺，确立了PRC2作为一种表观遗传机制，调节嗅觉神经元与鲍曼腺的谱系选择。
Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lineage decisions are not understood. Using mouse lesion models, we focused on defining the role of Polycomb repressive complexes (PRCs) in olfactory neurogenesis. PRC2 has a well-established role in developing tissues, orchestrating transcriptional programs via chromatin modification. PRC2 proteins are expressed in olfactory globose basal cells (GBCs) and nascent neurons. Conditional PRC2 loss perturbs lesion-induced neuron production, accompanied by altered histone modifications and misexpression of lineage-specific transcription factors in GBCs. De-repression of Sox9 in PRC2-mutant GBCs is accompanied by increased Bowman’s gland production, defining an unrecognized role for PRC2 in regulating gland versus neuron cell fate. Our findings support a model for PRC2-dependent mechanisms promoting sensory neuronal differentiation in an adult neurogenic niche. PRC2 proteins are expressed in olfactory basal cells in normal and injured conditions H3K27me3 marks genes active in neurogenesis and differentiation in olfactory basal cells PRC2 regulates choice between neuronal and non-neuronal lineages Ko et al. identified PRC2 as a mechanism regulating neurogenesis in the adult olfactory epithelium. PRC2-mutant olfactory basal cells lack key H3K27me3 marks and de-repress non-neural transcriptional programs, including Sox9. Lineage-traced Eed-deficient basal cells produce fewer neurons and more non-neuronal cells, including Bowman’s glands, establishing PRC2 as an epigenetic mechanism regulating olfactory neuron versus Bowman’s gland lineage choice.
登录
查看更多内容
影响因子：
2.5
作者：
Goldstein, Bradley J.;Goss, Garrett M.;Hatzistergos, Konstantinos E.;Rangel, Erika B.;Seidler, Barbara;Saur, Dieter;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
10.5
作者：
Cohen I;Bar C;Liu H;Valdes VJ;Zhao D;Galbo PM Jr;Silva JM;Koseki H;Zheng D;Ezhkova E
通讯作者：
Ezhkova E
影响因子：
13.6
作者：
通讯作者：
--
影响因子：
6.4
作者：
Choi, Rhea;Kurtenbach, Sarah;Goldstein, Bradley J.
通讯作者：
Goldstein, Bradley J.
影响因子：
4.5
作者：
Flora P;Li MY;Galbo PM Jr;Astorkia M;Zheng D;Ezhkova E
通讯作者：
Ezhkova E