ADAR1 mediated regulation of neural crest-derived melanocytes and Schwann cell development.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA525424 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8664483_1.fastq.gz | Fastqsanger.gz | |||
| SRR8664483_2.fastq.gz | Fastqsanger.gz | |||
| SRR8664484_1.fastq.gz | Fastqsanger.gz | |||
| SRR8664484_2.fastq.gz | Fastqsanger.gz | |||
| SRR8664485_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:We studied the physiological requirement of A-to-I RNA editing in neural crest cells. To this end, we generated mouse lines that undergo neural crest cell-specific deletion of Adar1 making use of the HtPAcre reporter. The mutants show global depigmentation and absence of myelin within the peripheral nerves. To assess global changes in gene regulation caused by conditional Adar1 deficiency in Schwann cells, a we performed transcriptomic analysis (RNA-seq) of sciatic nerves from independent samples from three control and three mutant animals at P4. The steady-state level of 3,009 mRNAs differed by at least two-fold in abundance between the two genotypes. Analysis of the 3,009 differentially-expressed mRNAs using the interferome database showed 75% of them to be within or associated with IFN type 1 or 2 signaling pathway. Interestingly, 34% of the RNA transcripts deregulated upon Adar1 invalidation are also deregulated upon nerve injury. Overall, our results suggest that Adar1 safeguards neural crest-derived cells from unwanted MDA5-mediated interferon production and chronic Interferon stimulated genes upregulation, with implications for the human diseases caused by ADAR1 mutations and neural crest development and linked-disorders.
2019-11-28 | GSE127795 | GEO
Project description:Msh homeobox 1 (MSX1) is a transcription factor implicated in neural crest specification. Ectopic expression of MSX1 reprograms mature melanocytes into a neural crest-like state as a single factor. MSX1-reprogrammed melanocytes lose pigmentation and become multipotent. To identify immediate targets of MSX1, we generated a tetracycline-inducible system (Tet-ON) in order to express MSX1 in primary melanocytes (iMSX1) in a clean and rapid way starting at defined time points and perform a global gene expression analysis.
2016-09-30 | GSE56957 | GEO
Project description:Schwann cell precursors (SCPs) are nerve-associated progenitors that not only can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate the atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest have similar transcriptional profiles characterized by a multipotent “hub” state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cell and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knock-out of the hub gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed toward distinct lineages.
2022-04-28 | GSE201257 | GEO
Project description:The neural crest gives rise to numerous cell types, dysfunction of which contributes to many disorders. Here, we report that adenosine deaminase acting on RNA (ADAR1), responsible for adenosine-to-inosine editing of RNA, is required for regulating the development of two neural crest derivatives: melanocytes and Schwann cells. Neural crest specific conditional deletion of Adar1 in mice leads to global depigmentation and absence of myelin from peripheral nerves, resulting from alterations in melanocyte survival and differentiation of Schwann cells, respectively. Upregulation of interferon stimulated genes precedes these defects, which are associated with the triggering of a signature resembling response to injury in peripheral nerves. Simultaneous extinction of MDA5, a key sensor of unedited RNA, rescues both melanocytes and myelin defects in vitro, suggesting that ADAR1 safeguards neural crest derivatives from aberrant MDA5-mediated interferon production. We thus extend the landscape of ADAR1 function to the fields of neural crest development and disease.
| S-EPMC6954203 | biostudies-literature
Project description:During development, neural crest cells are induced by signaling events at the neural plate border of all vertebrate embryos. Initially arising within the central nervous system, NC cells subsequently undergo an epithelial to mesenchymal transition to migrate into the periphery, where they differentiate into diverse cell types. Here we provide evidence that postnatal human epidermal keratinocytes, in response to FGF2 and IGF1 signals, can be reprogrammed toward a neural crest fate. Genome-wide transcriptome analyses show that keratinocyte-derived NC cells are similar to those derived from human embryonic stem cells. Moreover, they give rise in vitro and in vivo to neural crest derivatives such as peripheral neurons, melanocytes, Schwann cells and mesenchymal cells (osteocytes, chondrocytes, adipocytes and smooth muscle). By demonstrating that human KRT14+ keratinocytes can form neural crest cells, even from clones of single cells, our results have important implications in stem cell biology and regenerative medicine.
2016-11-20 | GSE72268 | GEO
Project description:Analysis of microarrays with transcriptome of human neural crest-originated stem cells (NCSC), highly metastatic BLM melanoma cell line and neonatal highly pigmented melanocytes (HPM) at whole genome scale demonstrated distinct differences among tested cell types.
2015-12-09 | E-MTAB-2401 | biostudies-arrayexpress
Project description:Neural stem cells (NSCs) are most commonly sourced from neural tissue such as the central nervous system or the enteric nervous system (ENS) of the gut. Emerging evidence has shown that adipose tissue contains its own complex nervous system consisting of sympathetic and sensory innervation. The entirety of the peripheral nervous system is the progeny of Wnt1-expressing cells of the embryonic neural crest. This includes the ENS, autonomic neurons, and Schwann cell precursors that provide peripheral glial cells. Counterintuitive to their name, however, embryonic Schwann cell precursors represent multipotent stem cells that migrate along embryonic nerve fibers and contribute to glial and non-glial cell populations, including melanocytes, neuroendocrine chromaffin cells, enteric neurons, sympathetic neurons and mesenchymal stem cells from the bone marrow, depending on local environmental cues. However, no equivalent progenitors are known to exist postnatally in the nerve fiber niche. Schwann cells have been demonstrated to give rise to enteric neurons postnatally, suggesting they retain neuronal progenitor properties and offer a potential source of NSCs for regenerative therapies. In this study, we compare the transcriptomic properties of neural crest-derived NSCs from the intestine (enteric neural progenitors) and the nerve fibers of the subcutaneous adipose tissue and evaluate the effects of different methods of NSC culture and isolation.
2022-05-31 | GSE200689 | GEO
Project description:Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel approach for studying human melanocyte development and disease. Here we report that timed exposure to activators of WNT, BMP and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders. Total RNA obtained from embryonic stem cells (ESCs), ESC-derived melanocyte progenitors, ESC-derived mature melanocytes, primary melanocytes, and disease-specific induced pluripotent stem cell-derived melanocytes.
2013-06-01 | E-GEOD-45226 | biostudies-arrayexpress
Project description:Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel approach for studying human melanocyte development and disease. Here we report that timed exposure to activators of WNT, BMP and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders. Total RNA obtained from a timecourse of Dual SMAD Inhibition (DSi), Neural Crest (NC), and Melanocyte (BE) differentiation of human embryonic stem cells in triplicate.
2013-06-01 | E-GEOD-45223 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines. The Illumina Infinium 27k Human DNA methylation Beadchip Rev B was used to obtain DNA methylation profiles across approximately 27,000 CpGs in the samples. Samples included 58 primary UM, 3 NUM and NCSC controls and 2 cell lines. Bisulphite converted DNA from the 63 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip Rev B
2013-02-14 | E-GEOD-44296 | biostudies-arrayexpress