MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex

Bian, Shan; Hong, Janet; Li, Qingsong; Schebelle, Laura; Pollock, Andrew; Knauss, Jennifer L.; Garg, Vidur; Sun, Tao

doi:10.1016/j.celrep.2013.03.037

Cited by 159 publications

(168 citation statements)

References 39 publications

(46 reference statements)

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“…A recent study of the functions of the miR-17-92 cluster has shown that miR-19 and miR-92a repress PTEN and Tbr2 (also known as Eomes), respectively, and suppress the transition from radial glial cells to intermediate progenitors (24). These two miRNAs have strong oncogenic effects by regulating PTEN and Bim (also known as Bcl2l11) (6,23).…”

Section: Discussionmentioning

confidence: 99%

The miR-17/106–p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells

Naka-Kaneda

Nakamura

Igarashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Neural stem/progenitor cell (NSPC) multipotency is highly regulated so that specific neural networks form during development. NSPCs cannot respond to gliogenic signals without acquiring gliogenic competence and decreasing their neurogenic competence as development proceeds. Coup-tfI and Coup-tfII are triggers of these temporal NSPC competence changes. However, the downstream effectors of Coup-tfs that mediate the neurogenic-togliogenic competence transition remain unknown. Here, we identified the microRNA-17/106 (miR-17/106)-p38 axis as a critical regulator of this transition. Overexpression of miR-17 inhibited the acquisition of gliogenic competence and forced stage-progressed NSPCs to regain neurogenic competence without altering the methylation status of a glial gene promoter. We also identified Mapk14 (also known as p38) as a target of miR-17/106 and found that Mapk14 inhibition restored neurogenic competence after the neurogenic phase. These results demonstrate that the miR-17/106-p38 axis is a key regulator of the neurogenic-to-gliogenic NSPC competence transition and that manipulation of this axis permits bidirectional control of NSPC multipotency.reatments of central nervous system (CNS) injury and diseases have become more promising with advances in modern medicine. Recent progress in stem cell biology has drawn attention to stem cells as innovative resources for transplantation therapies and individualized drug screenings (1, 2). Multipotent neural stem/progenitor cells (NSPCs) that give rise to all types of neural cells can now be readily obtained from induced pluripotent stem cells. However, specific and efficient induction of homogeneous target cell populations from NSPCs remains difficult because of the complex mechanisms that regulate NSPC development and differentiation. Therefore, further elucidation of how specific cell types can be generated from NSPCs is required to facilitate therapeutic applications.We recently used a newly developed embryonic stem cell (ESC)-derived neurosphere culture system to investigate the molecular mechanisms that govern NSPC differentiation (3). Although NSPCs are multipotent, and are thus able to differentiate into neurons and glial cells, neurogenesis largely precedes gliogenesis during CNS development in vertebrates. The neurogenesis-to-gliogenesis switch requires temporal identity transitions of NSPCs (4). Importantly, our neurosphere culture system recapitulates neural development in vivo. Using this system, we found that Coup-tfI and Coup-tfII (also known as Nr2f1 and Nr2f2, respectively) are critical molecular switches in the temporal identity transition of NSPCs (3). Remarkably, Coup-tfs do not repress neurogenesis or promote gliogenesis but, instead, change the competence of NSPCs. Although Coup-tfs permit alterations by changing the responsiveness of NSPCs to extrinsic gliogenic signals, the critical regulators and/or drivers of this process remain largely unknown. The aim of this study was to determine the molecular machinery underlying the neurogenicto-g...

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Section: Discussionmentioning

confidence: 99%

The miR-17/106–p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells

Naka-Kaneda

Nakamura

Igarashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Similarly, although not directly affecting the self-renewal capacity of radial glial cells (RGCs) within the developing cerebral cortex, Eomes is a key determinant of the differentiation of intermediate progenitor cells (IPCs), which comprise the RGC daughter transit amplifying progenitor population (Arnold et al, 2008b;Sessa et al, 2008). The transition from NSC to IPC is regulated by miR-92a through post-transcriptional regulation of Eomes (Bian et al, 2013). Eomes is also a crucial regulator of granule cell formation from NSCs in the dentate gyrus, both during development and in the adult.…”

Section: T-box Genes and Stem Cell Biologymentioning

confidence: 99%

The T-box gene family: emerging roles in development, stem cells and cancer

2014

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The T-box family of transcription factors exhibits widespread involvement throughout development in all metazoans. T-box proteins are characterized by a DNA-binding motif known as the T-domain that binds DNA in a sequence-specific manner. In humans, mutations in many of the genes within the T-box family result in developmental syndromes, and there is increasing evidence to support a role for these factors in certain cancers. In addition, although early studies focused on the role of T-box factors in early embryogenesis, recent studies in mice have uncovered additional roles in unsuspected places, for example in adult stem cell populations. Here, I provide an overview of the key features of T-box transcription factors and highlight their roles and mechanisms of action during various stages of development and in stem/progenitor cell populations.

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“…97 In the development of mouse neurocortex, the miR17-92 cluster controls neural progenitor cell proliferation by suppressing phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and the transcription factor Tbr 2. 98,99 Ablation of the miR17-92 cluster in OPCs during brain development reduces their proliferation, indicating that this cluster affects oligodendrogenesis. 100 Stroke robustly increases miR17-92 cluster expression in V/SVZ neural progenitor cells.…”

Section: Micrornas and Signaling Pathwaysmentioning

confidence: 99%

Function of neural stem cells in ischemic brain repair processes

Zhang

Chopp

2016

J Cereb Blood Flow Metab

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Hypoxic/ischemic injury is the single most important cause of disabilities in infants, while stroke remains a leading cause of morbidity in children and adults around the world. The injured brain has limited repair capacity, and thereby only modest improvement of neurological function is evident post injury. In rodents, embryonic neural stem cells in the ventricular zone generate cortical neurons, and adult neural stem cells in the ventricular-subventricular zone of the lateral ventricle produce new neurons through animal life. In addition to generation of new neurons, neural stem cells contribute to oligodendrogenesis. Neurogenesis and oligodendrogenesis are essential for repair of injured brain. Much progress has been made in preclinical studies on elucidating the cellular and molecular mechanisms that control and coordinate neurogenesis and oligodendrogenesis in perinatal hypoxic/ischemic injury and the adult ischemic brain. This article will review these findings with a focus on the ventricular-subventricular zone neurogenic niche and discuss potential applications to facilitate endogenous neurogenesis and thereby to improve neurological function post perinatal hypoxic/ischemic injury and stroke.

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MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex

Cited by 159 publications

References 39 publications

The miR-17/106–p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells

The miR-17/106–p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells

The T-box gene family: emerging roles in development, stem cells and cancer

Function of neural stem cells in ischemic brain repair processes

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