Molecular events in the cell types of the olfactory epithelium during adult neurogenesis.
Molecular events in the cell types of the olfactory epithelium during adult neurogenesis.
复制标题
DOI：
10.1186/1756-6606-6-49
复制
发表时间：
2013-11-22
期刊：
影响因子：
3.6
通讯作者：
McClintock TS
中科院分区：
文献类型：
--
作者：
Heron PM;Stromberg AJ;Breheny P;McClintock TS
成体神经发生是哺乳动物嗅觉上皮细胞动态平衡的基础，需要基因表达的重大变化才能从多能祖细胞产生成熟的嗅觉神经元(OSNs)。要理解这些动态事件，不仅需要确定涉及的基因，还需要确定表达每个基因的细胞类型。只有到那时，编码蛋白质的相互关系才能揭示控制成年嗅觉上皮可塑性的分子事件序列。在成年小鼠损伤诱导的OSN替换后5天的4,057个差异丰富的mRNAs中，有2,334个mRNAs在成熟的OSN中表达降低。在1,723个增加的mRNAs中，许多是由OSN以外的细胞类型表达的，并编码了参与细胞增殖和转录调控的蛋白质，这与基底细胞增殖的增加一致。其他的编码脂肪酸代谢和溶酶体蛋白，由渗透的巨噬细胞表达，帮助清除成熟OSN凋亡的碎片。未成熟OSN的mRNAs表现为二分性，如果它们支持OSN分化的早期事件(轴突起始、囊泡运输、细胞骨架组织和局部粘连)，则增加，但如果它们支持延续到成熟OSN的动态平衡过程(能量产生、轴突维持和蛋白质分解代谢)，则减少。负责将基底细胞转化为神经元的基因表达变化的复杂性，从基底细胞和未成熟的OSN表达的203个转录调节因子的丰富程度中可见一斑。在成人神经发生过程中引起的许多分子变化现在可以归因于OSN细胞谱系中的特定细胞事件，从而定义了这些神经元发展的新阶段。最值得注意的是，随着这些神经元的分化，未成熟OSN中的基因表达模式发生了特有的变化。最初的模式与向神经元形态(神经发生)的转变一致，后来的模式与神经元的稳态一致。总体而言，成人嗅神经发生过程中的基因表达模式与胚胎大脑的基因表达模式基本相似。
Adult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium. Of 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the 1,723 increased mRNAs, many were expressed by cell types other than OSNs and encoded proteins involved in cell proliferation and transcriptional regulation, consistent with increased basal cell proliferation. Others encoded fatty acid metabolism and lysosomal proteins expressed by infiltrating macrophages that help scavenge debris from the apoptosis of mature OSNs. The mRNAs of immature OSNs behaved dichotomously, increasing if they supported early events in OSN differentiation (axon initiation, vesicular trafficking, cytoskeletal organization and focal adhesions) but decreasing if they supported homeostatic processes that carry over into mature OSNs (energy production, axon maintenance and protein catabolism). The complexity of shifts in gene expression responsible for converting basal cells into neurons was evident in the increased abundance of 203 transcriptional regulators expressed by basal cells and immature OSNs. Many of the molecular changes evoked during adult neurogenesis can now be ascribed to specific cellular events in the OSN cell lineage, thereby defining new stages in the development of these neurons. Most notably, the patterns of gene expression in immature OSNs changed in a characteristic fashion as these neurons differentiated. Initial patterns were consistent with the transition into a neuronal morphology (neuritogenesis) and later patterns with neuronal homeostasis. Overall, gene expression patterns during adult olfactory neurogenesis showed substantial similarity to those of embryonic brain.
登录
查看更多内容
影响因子：
5.7
作者：
Calof, Anne L.
通讯作者：
Calof, Anne L.
影响因子：
7.8
作者：
Buchstaller, A;Kunz, S;Sonderegger, P
通讯作者：
Sonderegger, P
影响因子：
3.7
作者：
Fletcher ML
通讯作者：
Fletcher ML
影响因子：
4.6
作者：
Gokoffski, Kimberly K.;Wu, Hsiao-Huei;Calof, Anne L.
通讯作者：
Calof, Anne L.
影响因子：
64.8
作者：
Hansel, DE;Eipper, BA;Ronnett, GV
通讯作者：
Ronnett, GV