Evidence that nuclear factor IA inhibits repair after white matter injury.
Evidence that nuclear factor IA inhibits repair after white matter injury.
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DOI：
10.1002/ana.23590
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发表时间：
2012-08
影响因子：
11.2
通讯作者：
Deneen, Benjamin
中科院分区：
文献类型：
--
作者：
Fancy, Stephen P. J.;Glasgow, Stacey M.;Finley, Meggie;Rowitch, David H.;Deneen, Benjamin
慢性脱髓鞘可导致轴突病，并与人类神经系统疾病有关，如成人多发性硬化症（MS）和婴儿脑瘫。在这些疾病中，髓鞘再生受到少突胶质细胞祖细胞向产生髓鞘的少突胶质细胞分化受损的抑制。然而，与人类髓磷脂紊乱和髓磷脂再生相关的调节因子仍然知之甚少。在这里，我们研究了转录因子核因子-i - A （NFIA）在发育和再生髓鞘形成过程中少突胶质细胞祖细胞分化中的作用。NFIA在新生儿缺氧缺血性脑病（HIE）和多发性硬化症（MS）中的表达模式，以及小鼠的发育表达。利用溶卵磷脂模型，结合慢病毒NFIA的错误表达，进行了髓鞘再生过程中的功能研究。通过鸡和小鼠模型以及体外培养少突胶质细胞祖细胞，研究了NFIA在少突胶质细胞谱系发育中的作用。采用染色质免疫沉淀法和报告基因法评价NFIA功能的生化机制。在小鼠胚胎发育过程中，NFIA在少突胶质细胞祖细胞中表达，而在分化的少突胶质细胞中不表达。检测NFIA在新生儿HIE白质病变以及成人MS活跃性病变中的表达，发现它在少突胶质细胞祖细胞中表达相似，而在少突胶质细胞中表达相似。功能研究表明，NFIA通过直接抑制髓磷脂基因表达，足以抑制成人髓鞘再生和胚胎发育过程中少突胶质细胞祖细胞的分化。这些研究表明，NFIA参与控制少突胶质细胞祖细胞分化，并可能有助于抑制人髓鞘疾病的再髓鞘形成。
Chronic demyelination can result in axonopathy and is associated with human neurological conditions such as multiple sclerosis (MS) in adults and cerebral palsy in infants. In these disorders myelin regeneration is inhibited by impaired differentiation of oligodendrocyte progenitors into myelin-producing oligodendrocytes. However, regulatory factors relevant in human myelin disorders and in myelin regeneration remain poorly understood. Here we have investigated the role of the transcription factor Nuclear Factor-I A (NFIA) in oligodendrocyte progenitor differentiation during developmental and regenerative myelination NFIA expression patterns in human neonatal hypoxic-ischemic encephalopathy (HIE) and multiple sclerosis (MS), as well as developmental expression in mice were evaluated. Functional studies during remyelination were performed using a lysolecithin model, coupled with lentiviral misexpression of NFIA. The role of NFIA during oligodendrocyte lineage development was characterized using chick and mouse models and in vitro culture of oligodendrocyte progenitors. Biochemical mechanism of NFIA function was evaluated using chromatin immunopreciptation and reporter assays. NFIA is expressed in oligodendrocyte progenitors, but not differentiated oligodendrocytes during mouse embryonic development. Examination of NFIA expression in white matter lesions of human newborns with neonatal HIE, as well active MS lesions in adults, revealed that it is similarly expressed in oligodendrocyte progenitors and not oligodendrocytes. Functional studies indicate NFIA is sufficient to suppress oligodendrocyte progenitor differentiation during adult remyelination and embryonic development through direct repression of myelin gene expression. These studies suggest that NFIA participates in the control of oligodendrocyte progenitor differentiation and may contribute to the inhibition of remyelination in human myelin disorders.
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DOI：
10.1083/jcb.123.2.443
发表时间：
1993-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wight PA;Duchala CS;Readhead C;Macklin WB
通讯作者：
Macklin WB
DOI：
10.1073/pnas.1006496107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Sloane, J. A.;Batt, C.;Vartanian, T.
通讯作者：
Vartanian, T.
影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
158.5
作者：
Woodward, Lianne J.;Anderson, Peter J.;Inder, Terrie E.
通讯作者：
Inder, Terrie E.
影响因子：
25
作者：
Miller, Robert H.;Mi, Sha
通讯作者：
Mi, Sha