Transcriptional regulatory networks associated with self‐renewal and differentiation of neural stem cells

Yun, So Jeong; Byun, Kyunghee; Bhin, Jinhyuk; Oh, Jeehyun; Nhung, Le Thi Hong; Hwang, Daehee; Lee, Bong-Hee

doi:10.1002/jcp.22294

Cited by 18 publications

(16 citation statements)

References 160 publications

(160 reference statements)

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“…In addition, transcription factors were some of the other major classes of genes that are perturbed by SNL in the L4 DRG in our study and could play an important role in gene regulation following SNL. It is also interesting to note that expression of several transcription factors are known to be regulated by miRNAs [41], [42]. In depth analysis of individual genes and the mode of action of miRNAs targeting them is needed for further elucidation of miRNA activity on specific target mRNAs in neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

et al. 2011

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Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3′-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

et al. 2011

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“…via TGF- receptors), and signaling via receptor type tyrosine kinases (e.g. via Trk, FGF, or EGF receptors) 20,21 . Each of these signaling pathways is influenced by ubiquitination in one way or another.…”

Section: Ubiquitination In Neurogenesis and Gliogenesismentioning

confidence: 99%

The role of ubiquitylation in nerve cell development

2011

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| Nerve cell development in the brain is a tightly regulated process. The generation of neurons from precursor cells, their migration to the appropriate target sites, their extensive arborisation, and their integration into functional networks through synapse formation and refinement are governed by multiple interdependent signaling cascades. The function and turnover of proteins involved in these signaling cascades, in turn, are spatially and temporally controlled by ubiquitination. Recent advances have provided first insights into the highly complex and intricate molecular pathways that regulate ubiquitination during all stages of neural development and operate in parallel with other regulatory processes such as phosphorylation or cyclic nucleotide signaling.

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“…Stem cells are generally defined as immature cells with self-renewal competencies and the capability of differentiating into other cell types [1, 2]. Stem cells may be differentiated into a wide range of mature cell types, and because of their differential potential they may be classified into two types: embryonic stem cells (ESCs) and adult stem cells (ASCs) [3].…”

Section: Introductionmentioning

confidence: 99%

IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells

et al. 2014

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BackgroundThere has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.ResultsThe four derived NPCs showed a significantly higher expression of nestin than was shown by the negative control. Among the groups treated with growth factors, NPCs treated with IGF-1 showed the highest expression of nestin. Furthermore, NPCs derived using IGF-1 exhibited the highest cell proliferation and cell survival among the treated groups. The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups.ConclusionsOur results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs. This information will be beneficial in the long run for improving both cell-based and cell-free therapy for neurodegenerative diseases.

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Transcriptional regulatory networks associated with self‐renewal and differentiation of neural stem cells

Cited by 18 publications

References 160 publications

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

The role of ubiquitylation in nerve cell development

IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells

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