Sox2 protects neural stem cells from apoptosis via up-regulating survivin expression

2013 ◽  
Vol 450 (3) ◽  
pp. 459-468 ◽  
Author(s):  
Ruopeng Feng ◽  
Shixin Zhou ◽  
Yinan Liu ◽  
Daijun Song ◽  
Zhilin Luan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Brain Development ◽  
Molecular Mechanism ◽  
Cell Apoptosis ◽  
Survivin Expression ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Self Renewal

The transcription factor Sox2 [SRY (sex-determining region Y)-box 2] is essential for the regulation of self-renewal and homoeostasis of NSCs (neural stem cells) during brain development. However, the downstream targets of Sox2 and its underlying molecular mechanism are largely unknown. In the present study, we found that Sox2 directly up-regulates the expression of survivin, which inhibits the mitochondria-dependent apoptotic pathway in NSCs. Although overexpression of Sox2 elevates survivin expression, knockdown of Sox2 results in a decrease in survivin expression, thereby initiating the mitochondria-dependent apoptosis related to caspase 9 activation. Furthermore, cell apoptosis owing to knockdown of Sox2 can be rescued by ectopically expressing survivin in NSCs as well as in the mouse brain, as demonstrated by an in utero-injection approach. In short, we have found a novel Sox2/survivin pathway that regulates NSC survival and homoeostasis, thus revealing a new mechanism of brain development, neurological degeneration and such aging-related disorders.

scholarly journals Long non-coding RNA Peg13 attenuates the sevoflurane toxicity against neural stem cells by sponging microRNA-128-3p to preserve Sox13 expression

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243644
Author(s):  
Yunfeng Jiang ◽  
Yue Wang ◽  
Yu Sun ◽  
Hong Jiang
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Development ◽  
Luciferase Reporter ◽  
Luciferase Expression ◽  
Self Renewal ◽  
Over Expression ◽  
Non Coding Rna ◽  
Regulatory Effects

Background Exposure to anesthetics during brain development may impair neurological function, however, the mechanisms underlying anesthetic neurotoxicity are unclear. Recent studies indicate that long non-coding RNAs (lncRNAs) are crucial for regulating the functional brain development during neurogenesis. This study aimed to determine the regulatory effects and potential mechanisms of lncRNA Peg13 (Peg13) on sevoflurane exposure-related neurotoxicity against neural stem cells (NSCs). Methods Mouse embryotic NSCs were isolated and their self-renewal and differentiation were characterized by immunofluorescence. NSCs were exposed to 4.1% sevoflurane 2 h daily for three consecutive days. The potential toxicities of sevoflurane against NSCs were evaluated by neurosphere formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation and flow cytometry assays. The Peg13, miR-128-3p and Sox13 expression in NSCs were quantified. The potential interactions among Peg13, miR-128-3p and Sox13 were analyzed by luciferase reporter assay. The effects of Peg13 and/or miR-128-3p over-expression on the sevoflurane-related neurotoxicity and Sox13 expression were determined in NSCs. Results The isolated mouse embryotic NSCs displayed potent self-renewal ability and differentiated into neurons, astrocytes and oligodendrocytes in vitro, which were significantly inhibited by sevoflurane exposure. Sevoflurane exposure significantly down-regulated Peg13 and Sox13, but enhanced miR-128-3p expression in NSCs. Transfection with miR-128-3p mimics, but not the control, significantly mitigated the Peg13 or Sox13-regulated luciferase expression in 293T cells. Peg13 over-expression significantly reduced the sevoflurane-related neurotoxicity and increased Sox13 expression in NSCs, which were mitigated by miR-128-3p transfection. Conclusion Such data indicated that Peg13 mitigated the sevoflurane-related neurotoxicity by sponging miR-128-3p to preserve Sox13 expression in NSCs.

The Balance Between Self-Renewal and Differentiation of Human Neural Stem Cells Requires the Amyloid Precursor Protein

2021 ◽  
Author(s):  
Khadijeh Shabani ◽  
Julien Pigeon ◽  
Marwan Benaissa Touil Zariouh ◽  
Tengyuan Liu ◽  
Azadeh Saffarian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Self Renewal ◽  
Human Neural Stem Cells

scholarly journals Dissecting Hes-centered transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila

2020 ◽  
Author(s):  
Srivathsa S. Magadi ◽  
Chrysanthi Voutyraki ◽  
Gerasimos Anagnostopoulos ◽  
Evanthia Zacharioudaki ◽  
Ioanna K. Poutakidou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Transcription Factor ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Transcriptional Networks ◽  
Malignant Tumours ◽  
Stem Cell Maintenance

ABSTRACTNeural stem cells divide during embryogenesis and post embryonic development to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that in every asymmetric cell division progenitors send a Delta-Notch signal back to their sibling stem cells. Here we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. Our results suggest that Notch signalling sets up a network of mutually repressing stemness and anti-stemness transcription factors, which include Hes proteins and Zfh1, respectively. This mutual repression ensures robust transition to neuronal and glial differentiation and its perturbation can lead to malignant transformation.

scholarly journals Zika virus impairs growth in human neurospheres and brain organoids

2016 ◽  
Author(s):  
Patricia P Garcez ◽  
Erick C Loiola ◽  
Rodrigo F Madeiro da Costa ◽  
Luiza Higa ◽  
Pablo Trindade ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Brain ◽  
Brain Development ◽  
Zika Virus ◽  
Brain Cells ◽  
Zikv Infection ◽  
Human Neural Stem Cells ◽  
Human Brain Development

Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased dramatically in Brazil; however, causality between the widespread epidemic and malformations in fetal brains has not been confirmed. Here, we examine the effects of ZIKV infection in human neural stem cells growing as neurospheres and cerebral organoids. Using immunocytochemistry and electron microscopy, we show that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and cerebral organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development.

scholarly journals Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase–mediated damage of rat fetal neural stem cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeyong Yang ◽  
Jingjing Lv ◽  
Xingxing Li ◽  
Qiong Meng ◽  
Qiling Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Self Renewal

scholarly journals Demyelination Regulates the Circadian Transcription Factor BMAL1 to Signal Adult Neural Stem Cells to Initiate Oligodendrogenesis

Cell Reports ◽  
2020 ◽  
Vol 33 (7) ◽  
pp. 108394
Author(s):  
Suihong Huang ◽  
Ming Ho Choi ◽  
Hao Huang ◽  
Xin Wang ◽  
Yu Chen Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Adult Neural Stem Cells ◽  
Circadian Transcription
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