The role of Brn-4 in the regulation of neural stem cell differentiation into neurons

Shi, Jinhong; Jin, Guohua; Zhu, Huixia; Tian, Mei; Zhang, Xinhua; Qin, Jianbing; Tan, Xuefeng

doi:10.1016/j.neures.2010.01.007

Cited by 14 publications

(21 citation statements)

References 24 publications

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“…Overexpression of Brn4 elevates neuronal differentiation and maturation from NSCs, whereas suppression of expression of Brn4 using RNAi markedly decreases the number of newborn neurons (25,40,41). Brn4 coexpresses with MAP2 or ␤-tubulin-III in neurons, whereas almost all GFAP-positive astrocytes have a weak immunoreactive intensity of Brn4 (25). Taken together, Brn2 and Brn4 are required for neuronal differentiation and development.…”

Section: Discussionmentioning

confidence: 93%

“…The level of Brn4 is significantly up-regulated in newborn neurons originating from embryonic striatal NSCs stimulated by IGF-1 and BDNF (35). Overexpression of Brn4 elevates neuronal differentiation and maturation from NSCs, whereas suppression of expression of Brn4 using RNAi markedly decreases the number of newborn neurons (25,40,41). Brn4 coexpresses with MAP2 or ␤-tubulin-III in neurons, whereas almost all GFAP-positive astrocytes have a weak immunoreactive intensity of Brn4 (25).…”

Section: Discussionmentioning

confidence: 99%

“…The third one is to make the induced cells achieve the capacity to become neurons. The POU III family Brn2 and Brn4 conferred to the cells the tendency to become neurons (5,25). Therefore, we chose these eight factors for initial transdifferentiation trials and successfully produced hiNRPs.…”

Section: Neuronal Restricted Progenitors (Nrps) Represent a Type Of Tmentioning

confidence: 99%

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Direct Conversion of Human Fibroblasts into Neuronal Restricted Progenitors

Zou

Yan

Zhong

et al. 2014

Journal of Biological Chemistry

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Background: Neuronal restricted progenitors have not been generated from fibroblasts by transdifferentiation. Results: Human induced neuronal restricted progenitors (hiNRPs) were efficiently generated from fibroblasts by transfection of three defined factors: Sox2, c-Myc, and either Brn2 or Brn4. Conclusion: Unipotent neuronal restricted progenitors can be rapidly and efficiently produced from fibroblasts. Significance: This novel method will provide a new source of neurons for cellular replacement therapy of human neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Direct Conversion of Human Fibroblasts into Neuronal Restricted Progenitors

Zou

Yan

Zhong

et al. 2014

Journal of Biological Chemistry

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“…However, replacement of Oct6 with Oct8 in mice leads to severe defects in forebrain development (90), indicating that although overlapping functions exist for Oct6, 7 and 8, individual factors may have specific functions. Finally, Oct9 has been implicated in the regulation of striatal neuron precursor differentiation (149, 150). …”

Section: Functional Roles Of Oct In Specific Physiological Processesmentioning

confidence: 99%

Octamer-binding transcription factors: genomics and functions

Zhao¹

2013

Front Biosci

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The Octamer-binding proteins (Oct) are a group of highly conserved transcription factors that specifically bind to the octamer motif (ATGCAAAT) and closely related sequences that are found in promoters and enhancers of a wide variety of both ubiquitously expressed and cell type-specific genes. Oct factors belong to the larger family of POU domain factors that are characterized by the presence of a highly conserved bipartite DNA binding domain, consisting of an amino-terminal specific subdomain (POUS) and a carboxyl-terminal homeo-subdomain (POUH). Eleven Oct proteins have been named (Oct1-11), and currently, eight genes encoding Oct proteins (Oct1, Oct2, Oct3/4, Oct6, Oct7, Oct8, Oct9, and Oct11) have been cloned and characterized. Oct1 and Oct2 are widely expressed in adult tissues, while other Oct proteins are much more restricted in their expression patterns. Oct proteins are implicated in crucial and versatile biological events, such as embryogenesis, neurogenesis, immunity, and body glucose and amino acid metabolism. The aberrant expression and null function of Oct proteins have also been linked to various diseases, including deafness, diabetes and cancer. In this review, I will report both the genomic structure and major functions of individual Oct proteins in physiological and pathological processes.

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“…However, the outcome of the therapeutic effects of MSCs on neurogenesis and recovery of brain function is not sufficient, and remains to be further improved. Brn-4 is a transcription factor that plays a critical role in neuronal development [18,19,20,21], whereas the effects of Brn-4 overexpression in transplanted MSCs on AD are unknown. Therefore, increasing the levels of Brn-4 in MSCs may be examined to evaluate its effects on the outcome of MSC transplantation.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease

Liu

Wang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Alzheimer's disease (AD) is one of the most common dementias among aged people, and is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits. So far, this is no cure for AD. A therapeutic effect of transplantation of mesenchymal stem cells (MSCs) into murine model of AD has been reported, but remains to be further improved. Brn-4 is a transcription factor that plays a critical role in neuronal development, whereas the effects of Brn-4 overexpression in transplanted MSCs on AD are unknown. Methods: MSCs were isolated from mouse bone marrow and induced to overexpress antisense of miRNA-937 (as-miR-937) through adeno-associated virus (AAV)-mediated transduction, and purified by flow cytometry based on expression of a GFP co-transgene in the cells. The Brn-4 levels in mouse MSCs were examined in miR-937-modified MSCs by RT-qPCR and by Western blot. These miR-937-modified MSCs were then transplanted into an APP/PS1 transgenic AD model in mice. The effects of saline control, MSCs and asmiR-937 MSCs on AD mice were examined by deposition of amyloid-beta peptide aggregates (Aβ), social recognition test (SR), Plus-Maze Discriminative Avoidance Task (PM-DAT) and the levels of Brain-derived neurotrophic factor (BDNF) in the mouse brain. Results: MSCs expressed high levels of Brn-4 transcripts but low levels of Brn-4 protein. Poor protein vs mRNA levels of Brn-4 in MSCs appeared to result from the presence of high levels of miR-937 in MSCs. miR-937 inhibited translation of Brn-4 mRNA through binding to the 3'-UTR of the Brn-4 mRNA in MSCs. Expression of as-miR-937 significantly increased Brn-4 protein levels in MSCs. Transplantation of as-miR-937-expressing MSCs significantly reduced the deposition of Aβ, increased the levels of BDNF, and significantly improved the appearance in SR and PM-DAT in AD mice. Conclusion: Overexpression of as-miR-937 in MSCs may substantially improve the therapeutic effects of MSCs on AD, possibly through augmenting Brn-4 levels in MSCs.

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The role of Brn-4 in the regulation of neural stem cell differentiation into neurons

Cited by 14 publications

References 24 publications

Direct Conversion of Human Fibroblasts into Neuronal Restricted Progenitors

Direct Conversion of Human Fibroblasts into Neuronal Restricted Progenitors

Octamer-binding transcription factors: genomics and functions

Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease

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