In vivo intermittent hypoxia elicits enhanced expansion and neuronal differentiation in cultured neural progenitors.
In vivo intermittent hypoxia elicits enhanced expansion and neuronal differentiation in cultured neural progenitors.
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DOI：
10.1016/j.expneurol.2012.01.027
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发表时间：
2012-05
影响因子：
5.3
通讯作者：
Fuller, David D.
中科院分区：
文献类型：
--
作者：
Ross, Heather H.;Sandhu, Milap S.;Cheung, Tina F.;Fitzpatrick, Garrett M.;Sher, Warren J.;Tiemeier, Alexander J.;Laywell, Eric D.;Fuller, David D.
关键词：
在体外暴露的神经祖细胞（NPC）群体减少O2（如3%对20%）可以增加他们的增殖，存活和神经元分化。我们的目的是确定是否急性（<1小时），在体内暴露于间歇性缺氧（AIH）改变扩大和/或分化的后续体外培养的NPC从脑室下区（SVZ）。新生C57 BL/6小鼠（出生后第4天）暴露于AIH模式（20×1分钟;交替21%和10% O2）。AIH后立即分离SVZ组织，培养NPC群体，并作为神经球（NS）或作为贴壁单层细胞（MASC）进行测定。AIH可显著增加NS和MASC的增殖能力，并伴有增殖标志物Ki 67、MTT活性和低氧诱导因子1α（HIF-1α）信号的增加。肽阻断实验证实，HIF-1α下游蛋白对NS培养物中与终末分化相关的增殖和形态学变化都很重要。最后，免疫细胞化学和蛋白质印迹实验表明，AIH增加SVZ组织中神经元命运决定转录因子Pax 6的表达，这与培养的NS和MASC中神经元分化增加有关。我们的结论是，在体内AIH暴露可以提高随后在体外SVZ衍生的NPC培养的活力。因此，AIH方案可以提供一种在移植到受损的中枢神经系统之前“准备”NPC的方法。
In vitro exposure of neural progenitor cell (NPC) populations to reduced O2 (e.g. 3% versus 20%) can increase their proliferation, survival and neuronal differentiation. Our objective was to determine if an acute (<1 hr), in vivo exposure to intermittent hypoxia (AIH) alters expansion and/or differentiation of subsequent in vitro cultures of NPC from the subventricular zone (SVZ). Neonatal C57BL/6 mice (postnatal day 4) were exposed to an AIH paradigm (20×1 minute; alternating 21% and 10% O2). Immediately after AIH, SVZ tissue was isolated and NPC populations were cultured and assayed either as neurospheres (NS) or as adherent monolayer cells (MASC). AIH markedly increased the capacity for expansion of cultured NS and MASC, and this was accompanied by increases in a proliferation maker (Ki67), MTT activity and hypoxia-inducible factor-1α (HIF-1α) signaling in NS cultures. Peptide blockade experiments confirmed that proteins downstream of HIF-1α are important for both proliferation and morphological changes associated with terminal differentiation in NS cultures. Finally, immunocytochemistry and Western blotting experiments demonstrated that AIH increased expression of the neuronal fate determination transcription factor Pax6 in SVZ tissue, and this was associated with increased neuronal differentiation in cultured NS and MASC. We conclude that in vivo AIH exposure can enhance the viability of subsequent in vitro SVZ-derived NPC cultures. AIH protocols may therefore provide a means to “prime” NPC prior to transplantation into the injured central nervous system.
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DOI：
10.1016/j.bbrc.2006.03.015
发表时间：
2006-05-05
影响因子：
3.1
作者：
Greenberg, H;Ye, XB;Liu, SF
通讯作者：
Liu, SF
影响因子：
64.8
作者：
TEMPLE, S
通讯作者：
TEMPLE, S
影响因子：
5.2
作者：
Dale-Nagle EA;Hoffman MS;MacFarlane PM;Satriotomo I;Lovett-Barr MR;Vinit S;Mitchell GS
通讯作者：
Mitchell GS
影响因子：
2.3
作者：
Nanduri, Jayasri;Yuan, Guoxiang;Kumar, Ganesh K.;Semenza, Gregg L.;Prabhakar, Nanduri R.
通讯作者：
Prabhakar, Nanduri R.
影响因子：
5.3
作者：
Culver, Carolyn;Sundqvist, Anders;Rocha, Sonia
通讯作者：
Rocha, Sonia