Development-Inspired Reprogramming of the Mammalian Central Nervous System

Amamoto, Ryoji; Arlotta, Paola

doi:10.1126/science.1239882

Cited by 86 publications

(88 citation statements)

References 63 publications

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“…To examine the possible physiological relevance of gene expression deficiencies in CSB-deficient cells, we investigated cellular reprogramming of fibroblasts to neurons (13). This approach has previously been used to study diseases such as Alzheimer's disease (14) and Parkinson disease (15).…”

Section: Csb Is Required For Transdifferentiation Of Fibroblasts To Nmentioning

confidence: 99%

Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease

Wang

Chakravarty

Ranes

et al. 2014

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

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Significance Cockayne syndrome (CS) is an autosomal-recessive, multisystem disorder characterized by neurological disease, growth failure, developmental abnormalities, photosensitivity, and degeneration of organ systems such as the ear and eye, including cataracts. Most patients with CS carry mutations in Cockayne syndrome group B (CSB), best known for its role in transcription-coupled repair. Indeed, because various repair pathways are compromised in patient cells, CS is widely considered a genome instability syndrome. Here, we provide evidence from human and mouse cell models, as well as brain tissue from patients with CS, that the involvement of CSB in regulating gene expression can explain several features of CS. Together, our data suggest that dysregulation of gene regulatory networks rather than DNA repair defects may be the main cause of neurological symptoms in CS.

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Section: Csb Is Required For Transdifferentiation Of Fibroblasts To Nmentioning

confidence: 99%

Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease

Wang

Chakravarty

Ranes

et al. 2014

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

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“…The extraordinary interest in SoxB1 proteins and in particular the pluripotency factor Sox2 [SRY (sex determining region Y)-box 2] rests on a multitude of functional implications concerning basic and applied biomedical problems: it promotes neuroectodermal lineage selection in ES cells (Zhao et al 2004;Thomson et al 2011), plays a major role in reprogramming of non-neural cells to neural stem or precursor cells (Maucksch et al 2013;Amamoto and Arlotta 2014), is critically involved in vertebrate neurogenesis and glial cell development (Reiprich and Wegner, this issue;Hoffmann et al 2014), and orthologous proteins are found in the neurogenic regions of all animal phyla analyzed (see below). SOX2 haploinsufficiency in humans is associated with brain malformations as well as defects in multiple sensory systems including anophthalmia and hearing loss (Fantes et al 2003;Hagstrom et al 2005;Zenteno et al 2005).…”

Section: Sodium Channel Gene Expression and The Quest For The Master mentioning

confidence: 99%

Can the ‘neuron theory’ be complemented by a universal mechanism for generic neuronal differentiation

Ernsberger

2014

Cell Tissue Res

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With the establishment of the 'neuron theory' at the turn of the twentieth century, this remarkably powerful term was introduced to name a breathtaking diversity of cells unified by a characteristic structural compartmentalization and unique information processing and propagating features. At the beginning of the twenty-first century, developmental, stem cell and reprogramming studies converged to suggest a common mechanism involved in the generation of possibly all vertebrate, and at least a significant number of invertebrate, neurons. Sox and, in particular, SoxB and SoxC proteins as well as basic helix-loop-helix proteins play major roles, even though their precise contributions to progenitor programming, proliferation and differentiation are not fully resolved. In addition to neuronal development, these transcription factors also regulate sensory receptor and endocrine cell development, thus specifying a range of cells with regulatory and communicative functions. To what extent microRNAs contribute to the diversification of these cell types is an upcoming question. Understanding the transcriptional and post-transcriptional regulation of genes coding for cell type-specific cytoskeletal and motor proteins as well as synaptic and ion channel proteins, which mark differences but also similarities between the three communicator cell types, will provide a key to the comprehension of their diversification and the signature of 'generic neuronal' differentiation. Apart from the general scientific significance of a putative universal core instruction for neuronal development, the impact of this line of research for cell replacement therapy and brain tumor treatment will be of considerable interest.

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“…The first concerns the critical issue of unambiguous identification of a cell as being a neuron. On the other hand, it is currently not clear to which extent procedures to program neurons in vitro do and need to resemble in vivo development (Amamoto and Arlotta 2014).…”

mentioning

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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Development-Inspired Reprogramming of the Mammalian Central Nervous System

Cited by 86 publications

References 63 publications

Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease

Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease

Can the ‘neuron theory’ be complemented by a universal mechanism for generic neuronal differentiation

Deciphering the core instructions of neuronal differentiation

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