The role of microRNAs in human neural stem cells, neuronal differentiation and subtype specification

Stappert, Laura; Roese-Koerner, Beate; Brüstle, Oliver

doi:10.1007/s00441-014-1981-y

Cited by 89 publications

(87 citation statements)

References 176 publications

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“…40 Different types of coding and noncoding RNAs such as miRNAs and long non-coding RNAs (lncRNAs) are involved in these regulatory events. 41,42 Recently, several reports described important features of circRNA regulation in neuronal development, indicating possible regulatory involvement of circRNAs in these processes. 27,29,36 In general, circRNAs are up-regulated during neuronal differentiation in human and murine cell culture systems as well as in mouse primary neurons and porcine brains.…”

Section: Circrnas In Developmentmentioning

confidence: 99%

CircRNAs in the brain

2016

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Circular RNAs (circRNAs) are highly abundant and evolutionarily conserved non-coding RNAs produced by circularization of specific exons. Since their re-discovery as potential regulators of gene expression, thousands of circRNAs were detected in different tissues and cell types across most organisms. Accumulating data suggest key roles for them in the central nervous system. Neuronal-expressed RNAs are diverted to yield highly enriched CircRNAs in human, mouse, pig and flies, with many of them enriched in neuronal tissues. CircRNA levels are dynamically modulated in neurons, both during differentiation and following bursts of electrical activity, and accumulate with age, and many of them are enriched in synapses. Together, available data suggest that circRNAs have important roles in synaptic plasticity and neuronal function. This review covers current advances in the field and lays out hypotheses regarding functions of circRNAs in the brain as well as their putative involvement in initiation and progression of neurodegenerative processes.

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Section: Circrnas In Developmentmentioning

confidence: 99%

CircRNAs in the brain

2016

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“…let-7 and miR-200-modulated networks involve bHLH and Sox proteins (Trümbach and Prakash 2014;Rehfeld et al 2014, this issue). miR-9 and miR-124 affect different key regulators of neuronal development (Stappert et al 2014;Abernathy and Yoo 2014, this issue). miR-124 targets a range of effectors including the neuron-restrictive silencer factor (NRSF/REST), implicated in neuronal development and endocrine function (Thiel et al 2014;Stappert et al 2014, this issue) and the polypyrimidine tract binding proteins 1 (PTBP1) and consequentially PTBP2, RNA-binding proteins and splicing regulators involved in neuronal differentiation (Yano et al 2014;Abernathy and Yoo 2014, this issue).…”

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confidence: 99%

Deciphering the core instructions of neuronal differentiation

Ernsberger

2014

Cell Tissue Res

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The amazing field of Developmental Neuroscience has provided fascinating insights into mechanisms regulating the generation of a huge array of different neuron populations. The discovery of a large set of growth factors influencing cellular differentiation choices and transcription factors regulating expression of genes specific to progenitor and neuron populations has been instrumental. The analysis has failed, however, to establish a clear idea on the acquisition of the common structural as well as information-propagating and -processing neuronal features during neurogenesis. Moreover, it is not resolved how this is coordinated with the diversification of the distinct neuron populations.Focusing attention on the early developmental expression of shared molecular players involved in formation of the neuronal cytoskeleton, generation of action potentials and regulation of neurotransmitter release has begun to change the field. Together with the recognition of several layers in the coordination of gene expression extending from (1) modification of nuclear and chromatin organization to (2) action of transcription regulator complexes at enhancer and promoter sequences to (3) posttranscriptional regulation by powerful non-coding RNA/protein networks, a comprehensive picture of the route from neural progenitor to neuron takes shape.Fueled by the observation that a limited set of regulators from each of these layers has the potential to drive neuronal differentiation in stem cells or even from unrelated cell types such as fibroblasts, the finding of developmental expression patterns of genes coding for neuronal cytoskeletal and synaptic proteins conserved across vertebrate neuron populations prompts the question for a shared generic differentiation program. Involvement of some of those regulators and expression of certain target genes in sensory receptor and endocrine cell differentiation may define a group of related signalcommunicating cells and further refine the core of a neuronal differentiation program. Comparison to invertebrate neural development demonstrating related functions of orthologous regulators will decipher the evolutionary core instructions on 'how to build a neuron'. The consequences of such a basic comprehension of generic neuronal differentiation for stem cell-derived tissue replacement approaches, as well as the neuro-pathological and neuro-oncological clinic, are of particular interest.The exciting search for the mechanisms governing neuronal development has received additional momentum by the goal to predictably tailor programming and reprogramming routines for cell and tissue replacement techniques. Both basic and applied approaches have uncovered or employed, respectively, regulatory schemes related to the diversification of the enormous variety of neuron classes. In order to generate a specific type of neuron in vitro this procedure has already proven successful. Yet Ninkovic and Götz (2014, this issue) discuss the question whether application of a common principle of neuronal differentia...

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“…In general, miR-124, miR-125b, miR-137, miR-7 are contributing to neuronal differentiation, whereas miR-134, miR-184 are effective in maintaining neural stem cells at the undifferentiated status [15,16]. Indeed, miR-124 has been demonstrated to be the most abundantly expressed in adult brain [17] and is upregulated during neural progenitor cell differentiation and neuronal maturation [18].…”

Section: Mirnas In the Central Nervous System (Cns)mentioning

confidence: 99%