Leukemia inhibitory factor is essential for subventricular zone neural stem cell and progenitor homeostasis as revealed by a novel flow cytometric analysis.
Leukemia inhibitory factor is essential for subventricular zone neural stem cell and progenitor homeostasis as revealed by a novel flow cytometric analysis.
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DOI：
10.1159/000345155
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发表时间：
2012
影响因子：
2.9
通讯作者：
Levison SW
中科院分区：
文献类型：
--
作者：
Buono KD;Vadlamuri D;Gan Q;Levison SW
干细胞依赖于微环境产生的细胞外信号，这决定了它们自我更新、扩展和分化的能力。必须有灵敏且可重复的方法来量化或分离这些干细胞和祖细胞，以了解它们的内在特性以及外在信号如何调节它们的发育。然而，干细胞很难与多能祖细胞区分开来，因为多能祖细胞的外观和行为可能与干细胞相似。在这里，我们使用 CD133、LeX、CD140a、NG2 定义了 4 色流式细胞术面板来定义 NSC 以及 4 类多能祖细胞和 3 类双能祖细胞，其中一些以前未曾描述过。我们对 LIF 进行了功能获得和丧失的研究，结果显示 LIF 缺失小鼠中 NSC（多能神经前体细胞的一个子集）和未成熟少突胶质细胞的消耗。功能获得研究表明，LIF 增加了这些前体的丰度。我们的研究还表明，这些 NP 在体外繁殖时对 LIF 和 CNTF 以及 EGF、FGF-2 和 PDGF 有不同的需求。令人惊讶的是，相关细胞因子 CNTF 在增加 NSC 方面不如 LIF 有效，但在增加 PDGF 反应性多能前体方面比 LIF 更有效。最后，我们发现 LIF 增加了核心转录因子的表达：Klf4、Fbx15、Nanog、Sox2 和 c-Myc。总而言之，我们的 FACS 分析表明，新生儿 SVZ 的异质性比之前怀疑的要高得多，我们的研究为调节其自我更新和增殖的信号和机制提供了新的见解。
Stem cells rely on extracellular signals produced by the niche, which dictate their ability to self-renew, expand and differentiate. It is essential to have sensitive and reproducible methods of either quantifying or isolating these stem cells and progenitors to understand their intrinsic properties and how extrinsic signals regulate their development. However, stem cells are difficult to distinguish from multipotential progenitors, which may look and act like them. Here we define a 4-color flow cytometry panel using CD133, LeX, CD140a, NG2 to define an NSC as well as 4 classes of multipotential progenitors and 3 classes of bipotential progenitors, several of which have not been previously described. We performed gain and loss of function studies for LIF and show a depletion of NSCs, a subset of multipotential neural precursors and immature oligodendrocytes in LIF null mice. Gain of function studies showed that LIF increased the abundance of these precursors. Our studies also show that these NPs have differential requirements for LIF and CNTF and for EGF, FGF-2 and PDGF for their propagation in vitro. Surprisingly, the related cytokine, CNTF was less potent than LIF in increasing the NSCs and more potent than LIF in increasing the PDGF responsive multipotential precursors. Finally, we show that LIF increases the expression of the core transcription factors: Klf4, Fbx15, Nanog, Sox2 and c-Myc. Altogether our FACS analyses reveal that the neonatal SVZ is far more heterogeneous than previously suspected and our studies provide new insights into the signals and mechanisms that regulate their self-renewal and proliferation.
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DOI：
10.1073/pnas.0710000105
发表时间：
2008-01-22
影响因子：
11.1
作者：
Coskun, Volkan;Wu, Hao;Sun, Yi E.
通讯作者：
Sun, Yi E.
影响因子：
5.3
作者：
Chojnacki, Andrew;Mak, Gloria;Weiss, Samuel
通讯作者：
Weiss, Samuel
影响因子：
5.3
作者：
Chojnacki, A;Weiss, S
通讯作者：
Weiss, S
DOI：
10.1083/jcb.200702031
发表时间：
2007-12-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jablonska B;Aguirre A;Vandenbosch R;Belachew S;Berthet C;Kaldis P;Gallo V
通讯作者：
Gallo V
影响因子：
5.3
作者：
Mallon, BS;Shick, HE;Macklin, WB
通讯作者：
Macklin, WB