Transcriptional profiling of fetal hypothalamic TRH neurons
Transcriptional profiling of fetal hypothalamic TRH neurons
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DOI：
10.1186/1471-2164-12-222
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发表时间：
2011-05-10
期刊：
影响因子：
4.4
通讯作者：
Charli, Jean-Louis
中科院分区：
文献类型：
--
作者：
Guerra-Crespo, Magdalena;Perez-Monter, Carlos;Charli, Jean-Louis
背景资料：在小鼠下丘脑发育期间，不同的神经内分泌细胞表型在重叠时期产生;这表明细胞类型特异性发育程序可以实现完全成熟。包括细胞增殖、细胞周期退出以及基因表达的表观遗传调节在内的程序之间的平衡是神经发生的特征。促甲状腺激素释放激素（TRH）是一种调节能量稳态和自主反应的肽。为了更好地了解TRH神经元发育的分子机制，我们进行了全基因组范围的研究，其转录组在胎儿下丘脑development.Results：在原代培养，TRH细胞占2%的总胎儿下丘脑细胞群。为了纯化这些细胞，我们利用了Trh基因调控区的跨越-774至+84 bp的片段赋予TRH细胞中绿色荧光蛋白（GFP）的特异性表达的事实。通过荧光激活细胞分选纯化转染的TRH细胞，合并各种细胞制备物，并将其转录组与GFP-下丘脑细胞的转录组进行比较。TRH细胞经历分化的终末阶段，表达与蛋白质生物合成、细胞内信号传导和转录控制有关的基因。在转录相关的成绩单，我们确定了转录因子Klf 4，Klf 10和Atf 3，这是以前uncharacterized内下丘脑.Conclusion：据我们所知，这是第一个报告确定转录本具有潜在的重要作用，在发展过程中的一个特定的下丘脑神经元表型。这种基因组规模的研究形成了一个合理的基础，以确定可能参与下丘脑TRH神经元的发育和功能的基因。
Background: During murine hypothalamic development, different neuroendocrine cell phenotypes are generated in overlapping periods; this suggests that cell-type specific developmental programs operate to achieve complete maturation. A balance between programs that include cell proliferation, cell cycle withdrawal as well as epigenetic regulation of gene expression characterizes neurogenesis. Thyrotropin releasing hormone (TRH) is a peptide that regulates energy homeostasis and autonomic responses. To better understand the molecular mechanisms underlying TRH neuron development, we performed a genome wide study of its transcriptome during fetal hypothalamic development.Results: In primary cultures, TRH cells constitute 2% of the total fetal hypothalamic cell population. To purify these cells, we took advantage of the fact that the segment spanning -774 to +84 bp of the Trh gene regulatory region confers specific expression of the green fluorescent protein (GFP) in the TRH cells. Transfected TRH cells were purified by fluorescence activated cell sorting, various cell preparations pooled, and their transcriptome compared to that of GFP-hypothalamic cells. TRH cells undergoing the terminal phase of differentiation, expressed genes implicated in protein biosynthesis, intracellular signaling and transcriptional control. Among the transcription-associated transcripts, we identified the transcription factors Klf4, Klf10 and Atf3, which were previously uncharacterized within the hypothalamus.Conclusion: To our knowledge, this is one of the first reports identifying transcripts with a potentially important role during the development of a specific hypothalamic neuronal phenotype. This genome-scale study forms a rational foundation for identifying genes that might participate in the development and function of hypothalamic TRH neurons.