Differential expression of a stress‐regulated gene Nr4a2 characterizes early‐ and late‐born hippocampal granule cells
Differential expression of a stress‐regulated gene Nr4a2 characterizes early‐ and late‐born hippocampal granule cells
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应激调节基因 Nr4a2 的差异表达是早生和晚生海马颗粒细胞的特征
DOI：
10.1002/hipo.23045
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Chiba Hideki
中科院分区：
文献类型：
--
作者：
Imura Tetsuya;Kobayashi Yasuyuki;Suzutani Ken;Ichikawa‐Tomikawa Naoki;Chiba Hideki
神经祖细胞在围产期获得GFAP表达，并在整个成年期继续在海马齿状回产生颗粒细胞（GC）。与早期出生的GC相比，GFAP+祖细胞衍生的晚期出生的GC的细胞特征仍然未知。使用小鼠的遗传命运图，我们表明早期和晚期出生的GC分别集中在GC层的外侧和内侧。然后，我们确定核孤儿受体Nr4A2优先由早期出生的GC表达。Nr4a2的表达在束缚应激和糖皮质激素水平的反应中动态调节，表明Nr4a2是GC中的应激调节基因。急性应激抑制但慢性应激反过来诱导GC中Nr4a2的表达。新生成的GC的存活受到慢性束缚应激的损害，中年后的长期应激降低了老年小鼠中晚期出生的GC的比例。因此，早期和晚期出生的GC表现出特征性的解剖分布，差异基因表达和对环境应激的不同反应。
Neural progenitors acquire GFAP expression during the perinatal period and continue to generate granule cells (GCs) in the hippocampal dentate gyrus throughout adulthood. Cellular characteristics of GFAP+ progenitor‐derived late‐born GCs in comparison with early‐born GCs remain unknown. Using genetic fate mapping in mice, we show that early‐ and late‐born GCs are concentrated in the outer and inner side of the GC layer, respectively. We then identify that a nuclear orphan receptor Nr4A2 is preferentially expressed by early‐born GCs. Nr4a2 expression is dynamically regulated in response to restraint stress and glucocorticoid levels, indicating that Nr4a2 is a stress‐regulated gene in GCs. Acute stress suppresses but chronic stress conversely induces Nr4a2 expression in GCs. The survival of newly generated GCs is impaired by chronic restraint stress and long‐term stress after middle age decreases the proportion of late‐born GCs in aged mice. Thus, early‐ and late‐born GCs exhibit characteristic anatomical distribution, differential gene expression, and distinct response to environmental stress.