A Shared Transcriptional Identity for Forebrain and Dentate Gyrus Neural Stem Cells from Embryogenesis to Adulthood
A Shared Transcriptional Identity for Forebrain and Dentate Gyrus Neural Stem Cells from Embryogenesis to Adulthood
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DOI：
10.1523/eneuro.0271-21.2021
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发表时间：
2022-01-01
期刊：
影响因子：
3.4
通讯作者：
Miller, Freda D.
中科院分区：
文献类型：
--
作者：
Borrett, Michael J.;Innes, Brendan T.;Miller, Freda D.
成体神经干细胞（NSCs）存在于哺乳动物脑内两个不同的小生境中，即前脑侧脑室的脑室-脑室下区（V-SVZ）和海马齿状回的颗粒下区（SGZ）。它们被认为是分子上不同的，因为V-SVZ NSC产生抑制性嗅球（OB）中间神经元，而SGZ NSC产生兴奋性齿状颗粒神经元。在这里，我们通过使用单细胞转录数据直接比较从胚胎发育到成年的V-SVZ和SGZ NSC来询问是否如此。我们发现，这两个神经干细胞群体的胚胎放射状神经胶质前体（RP）的父母是非常相似的，但差异表达的一小群基因参与γ-氨基丁酸能神经发生。这些不同的RP然后经历类似的逐渐过渡到休眠的成年NSC状态在出生后的前三周。这种休眠状态涉及维持活性、增殖、前分化状态的基因的转录关闭以及参与感测和调节其生态位环境的基因的诱导。此外，当重新激活，以产生成年出生的后代，这两个人口重新获得一个发展样的状态和重新表达proneurogenic基因。因此，V-SVZ和SGZ NSC在其整个生命周期中共享共同的转录状态，并通过类似的轨迹过渡到休眠和休眠。
Adult neural stem cells (NSCs) reside in two distinct niches in the mammalian brain, the ventricular-subventricular zone (V-SVZ) of the forebrain lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. They are thought to be molecularly distinct since V-SVZ NSCs produce inhibitory olfactory bulb (OB) interneurons and SGZ NSCs excitatory dentate granule neurons. Here, we have asked whether this is so by directly comparing V-SVZ and SGZ NSCs from embryogenesis to adulthood using single-cell transcriptional data. We show that the embryonic radial glial precursor (RP) parents of these two NSC populations are very similar, but differentially express a small cohort of genes involved in glutamatergic versus GABAergic neurogenesis. These different RPs then undergo a similar gradual transition to a dormant adult NSC state over the first three postnatal weeks. This dormancy state involves transcriptional shutdown of genes that maintain an active, proliferative, prodifferentiation state and induction of genes involved in sensing and regulating their niche environment. Moreover, when reactivated to generate adult-born progeny, both populations reacquire a development-like state and re-express proneurogenic genes. Thus, V-SVZ and SGZ NSCs share a common transcriptional state throughout their lifespans and transition into and out of dormancy via similar trajectories.