Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2.
Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2.
复制标题
DOI：
10.3389/fncel.2017.00186
复制
发表时间：
2017
影响因子：
5.3
通讯作者：
Tirone F
中科院分区：
文献类型：
--
作者：
Micheli L;Ceccarelli M;Gioia R;D'Andrea G;Farioli-Vecchioli S;Costanzi M;Saraulli D;Cestari V;Tirone F
细胞增殖和分化是相互依赖的过程。在这里，我们要问神经祖细胞扩增和分化这两个过程在多大程度上是功能分离的。因此，我们分析了是否有可能通过适当时间的不同刺激诱导齿状回祖细胞的增殖和/或分化，来挽救齿状回祖细胞终末分化的缺陷，而齿状回是一生中产生新神经元的地方。我们使用Tis21敲除小鼠作为模型，其齿状回神经元，正如我们和其他人所证明的那样，具有终末分化的内在缺陷。我们首先测试了两种增殖性和分化性神经源性刺激的效果，一种是药理学刺激（氟西汀），另一种是认知刺激（莫里斯水迷宫（MWM）训练）。两者均能有效增加齿状回新神经元的产生数量，氟西汀也能减少Tis21敲除的齿状回祖细胞的s期长度，提高对照细胞的分化率，但两者均不能提高分化缺陷率。相反，通过在体内感染增殖的齿状回祖细胞，逆转录病毒可以沉默Id3（一种神经分化抑制剂）或表达NeuroD2（一种在终分化的齿状回神经元中表达的前神经基因），完全挽救了末端分化的缺陷。这是首次证明NeuroD2或Id3的沉默可以激活齿状回神经元的分化，弥补分化缺陷。它还强调了齿状回神经元的分化速率是如何在几个水平上受到遗传调节的，并且神经干细胞/祖细胞扩增的神经源性刺激本身可能不足以改变这一速率。
Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the other cognitive (the Morris water maze (MWM) training). Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.
登录
查看更多内容
影响因子：
2.6
作者：
Caiaffo V;Oliveira BD;de Sá FB;Evêncio Neto J
通讯作者：
Evêncio Neto J
影响因子：
9.8
作者：
Dupret D;Fabre A;Döbrössy MD;Panatier A;Rodríguez JJ;Lamarque S;Lemaire V;Oliet SH;Piazza PV;Abrous DN
通讯作者：
Abrous DN
影响因子：
4.3
作者：
Epp JR;Chow C;Galea LA
通讯作者：
Galea LA
影响因子：
5.3
作者：
Farioli-Vecchioli S;Ceccarelli M;Saraulli D;Micheli L;Cannas S;D'Alessandro F;Scardigli R;Leonardi L;Cinà I;Costanzi M;Mattera A;Cestari V;Tirone F
通讯作者：
Tirone F
DOI：
10.3233/bpl-150020
发表时间：
2015-10-09
期刊：
Brain plasticity (Amsterdam, Netherlands)
影响因子：
--
作者：
Bolijn S;Lucassen PJ
通讯作者：
Lucassen PJ