Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment

Selvaraj, Prabhuanand; Xiao, Lan; Lee, Cheol; Murthy, Saravana R. K.; Cawley, Niamh X.; Lane, Malcolm V.; Merchenthaler, Istvån; Ahn, Sang‐Hyeon; Loh, Y. Peng

doi:10.1002/stem.2511

Cited by 31 publications

(32 citation statements)

References 88 publications

(124 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the results also showed that the DEGs we re associated with regulation of the ERK1 and ERK2 cascade. A previous study revealed that a novel neurotrophic factor, NF-α1, can induce the differentiation of NSCs to astrocytes by activating the ERK1/2-Sox9 signaling path way [31]. Folate is also involved in regulating the proliferation and reduced apoptosis of NSCs accompanied by ERK1/2 phosphorylation [32].…”

Section: Discussionmentioning

confidence: 99%

Identification and Verification of Candidate Genes Regulating Neural Stem Cells Behavior Under Hypoxia

Shi

Wei

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Neural stem cells (NSCs) reside in a hypoxic environment, and hypoxia plays an important role in their development and differentiation. This study aimed to explore the underlying mechanisms by which hypoxia affects NSC behavior. Methods: In the current study, we downloaded the gene expression dataset GSE68572 and identified the differentially expressed genes (DEGs) by analyzing high-throughput gene expression in hypoxic and normoxic NSCs. Subsequently, we analyzed these data using a combined bioinformatics approach and predicted the microRNAs (miRNAs) targeting the key gene using miRNA databases. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of the top five DEGs. Results: In total, 1347 genes were identified as DEGs. We identified the predominant gene ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways that were significantly over-represented in the hypoxic NSCs. A protein–protein interaction network he identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for liver cancer the top 10 core genes. Vascular endothelial growth factor A (VEGFA) had the highest degree and may be the key gene concerning NSC behavior under hypoxia. Further validation of the top five DEGs by qRT-PCR demonstrated that four DEGs were significantly higher and one DEG was significantly lower in the hypoxic group than in the control group. Seven miRNAs were predicted and proved to target VEGFA. Conclusion: This preliminary study can prompt the understanding of the molecular mechanisms by which hypoxia has an impact on NSC behavior and can help to optimize stem cell therapies for central nervous system injuries and diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification and Verification of Candidate Genes Regulating Neural Stem Cells Behavior Under Hypoxia

Shi

Wei

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Membranes were probed overnight at 50°C with the DIG-labeled mCPE probe directed to the mCPE open reading frame (ORF). After 6 washes (described in the Ambion protocol), the membranes were processed for immunodetection by using an anti-DIG-AP antibody (1:10,000; F. Hoffmann-La Roche) and visualized with disodium 3-(4-methoxyspiro {1,2-dioxetane-3,29-(59-chloro)tricyclo [3.3.1.1 3,7 ]decan}-4yl)phenyl phosphate (CSPD; 1:100, 11655884001; Roche) against X-film.…”

Section: Northern Blot Analysismentioning

confidence: 99%

“…The enzymatic activity of CPE-DN was analyzed by HPLC. A) Sequence of ACTH (1-17)-(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) showing cleavage sites for CPE at C-terminal basic amino acid residues. B) Lysates from CPE-WT, CPE-DN, or control adenovirus-infected COS-7 cells were incubated for 24 h with ACTH (1-17), with and without cobalt and/or GEMSA, and the enzymatically processed products were analyzed by HPLC.…”

mentioning

confidence: 99%

“…B) Lysates from CPE-WT, CPE-DN, or control adenovirus-infected COS-7 cells were incubated for 24 h with ACTH (1-17), with and without cobalt and/or GEMSA, and the enzymatically processed products were analyzed by HPLC. At pH 5.5, CPE-WT generated different peptide products: ACTH (1-16), ACTH (1-15), and ACTH(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), which were induced by cobalt and inhibited by GEMSA (i). CPE-DN generated only 1 peptide product, ACTH (1-16) (ii); whereas control lysate did not show any peptide product (iii).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cloning, gene regulation, and neuronal proliferation functions of novel N‐terminal–truncated carboxypeptidase E/neurotrophic factor‐αl variants in embryonic mouse brain

et al. 2018

Self Cite

View full text Add to dashboard Cite

Carboxypeptidase E (CPE), an exopeptidase involved in proneuropeptide processing, is also a neurotrophic factor, named neurotrophic factor-α1 (NF-α1) and has important roles in neuroprotection, stem cell differentiation, and neurite outgrowth, independent of enzymatic activity. Additionally, an N-terminal-truncated CPE/NF-α1 variant, (CPE/NF-α1)-ΔN, proposed from bioinformatic analysis of GenBank (National Center for Biotechnology Information, Bethesda, MD, USA) DNA sequences and encoding a 40-kDa protein, has been found to be exclusively expressed in embryonic neurons. To investigate the function of (CPE/NF-α1)-ΔN in neurodevelopment, we first cloned (CPE/NF-α1)-ΔN transcripts from an embryonic mouse brain. A rapid amplification of cDNA ends assay, DNA sequencing, and Northern blot revealed 1.9- and 1.73-kb transcripts, which encoded 47- and 40-kDa (CPE/NF-α1)-ΔN proteins, respectively. Those proteins were expressed in embryonic mouse brain. Expression of the 2 (CPE/NF-α1)-ΔN mRNAs surged at embryonic d 10.5, correlating with the time of neurogenesis in the developing brain and also at postnatal d 1. HT22 cells, a mouse hippocampal cell line, transduced with 40 kDa (CPE/NF-α1)-ΔN up-regulated expression of genes involved in embryonic neurodevelopment: insulin-like growth factor binding protein 2 ( IGFBP2), death-associated protein 1, and ephrin A1, which regulate proliferation, programmed cell death, and neuronal migration, respectively. HT22 cells and embryonic cortical neurons overexpressing 40 kDa (CPE/NF-α1)-ΔN exhibited enhanced proliferation, which was inhibited by IGFBP2 short interfering RNA treatment. Thus, 40 kDa (CPE/NF-α1)-ΔN has an important, enzymatically independent role in the regulation of genes critical for neurodevelopment.-Xiao, L., Yang, X., Sharma, V. K., Loh, Y. P. Cloning, gene regulation, and neuronal proliferation functions of novel N-terminal-truncated carboxypeptidase E/neurotrophic factor-αl variants in embryonic mouse brain.

show abstract

“…The Wnt signaling pathway has been implicated in the modulation of self‐renew and cell fate in diverse stem cells (Aubert et al, ; Anakwe et al, ; Bi et al, ; Cain and Manilay, ; Huang et al, ; Lee et al, ; Selvaraj et al, ; Leiros et al, ). The secreted Frizzled‐related proteins (SFRPs) are considered to be the endogenous antagonists of the Frizzled receptors of Wnt proteins, which contain a homologous region to Frizzled but lack a transmembrane domain to transmit signals (Lee et al, ).…”

Section: Introductionmentioning

confidence: 99%

SFRP2 enhanced the adipogenic and neuronal differentiation potentials of stem cells from apical papilla

Xiao

Dong

et al. 2017

Cell Biology International

View full text Add to dashboard Cite

Dental tissue-derived mesenchymal stem cells (MSCs) are easily obtained and considered as a favorable cell source for tissue engineering, but the regulation of direct differentiation is unknown, which restricts their application. The present study investigated the effect of SFRP2, a Wnt signaling modulator, on MSC differentiation using stem cells from apical papilla (SCAPs). The cells were cultured in specific inducing medium for adipogenic, neurogenic, or chondrogenic differentiation. Over-expression of SFRP2 via retroviral infection enhanced the adipogenic and neurogenic differentiation of SCAPs. While inhibit of Wnt pathway by IWR1-endo could enhance the neurogenic differentiation potentials of SCAPs, similar with the function of SFRP2. In addition, over-expression of SFRP2 up-regulated the expression of stemness-related genes SOX2 and OCT4. Furthermore, SOX2 and OCT4 expression was significantly inhibited after lentiviral silencing of SFRP2 in SCAPs. Therefore, our results suggest that SFRP2 enhances the adipogenic and neurogenic differentiation potentials of SCAPs by up-regulating SOX2 and OCT4. Moreover, the effect of SFRP2 in neurogenic differentiation of SCAPs maybe also associated with Wnt inhibition. Our results provided useful information about the molecular mechanism underlying directed differentiation in dental tissue-derived MSCs.

show abstract

Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment

Cited by 31 publications

References 88 publications

Identification and Verification of Candidate Genes Regulating Neural Stem Cells Behavior Under Hypoxia

Identification and Verification of Candidate Genes Regulating Neural Stem Cells Behavior Under Hypoxia

Cloning, gene regulation, and neuronal proliferation functions of novel N‐terminal–truncated carboxypeptidase E/neurotrophic factor‐αl variants in embryonic mouse brain

SFRP2 enhanced the adipogenic and neuronal differentiation potentials of stem cells from apical papilla

Contact Info

Product

Resources

About