Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat neural progenitor cells and their differentiation into neurons and astrocytes

ABSTRACT: Experiment comparing Low-density, CCg derived, progenitors (LDP) with high-density progenitors (HDP), and neurons (LDN) and astrocytes (LDA) derived from the LDP condition

ORGANISM(S): Rattus norvegicus

SUBMITTER: James Bradley Aimone

PROVIDER: E-GEOD-2499 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition.

Muotri Alysson R AR Chu Vi T VT Marchetto Maria C N MC Deng Wei W Moran John V JV Gage Fred H FH

Nature 20050601 7044

Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human LINE-1 (for long interspersed nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fa ...[more]

PMID: 15959507

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Project description:Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains as well as light chains. However, their edification is different from the ones found in B cells and resembles aberrant immunoglobulins as observed in several cancers. Moreover, the complete enzymatic V(D)J recombination complex has also been identified in astrocytes. In addition, the constant heavy chain is also present in astrocytes adult rats, whereas in primary astrocytes from human fetal astrocytes we identified constant and variable kappa chains as well as the substitution lambda chains known to be involved in pre-B cells. To gather insights into the function of these neural IgGs, CRISPR-Cas9 IgG2B constant heavy chain (IgH6), overexpression, proximal labeling of rat astrocytes IgH6 and targets identification through 2D gels were performed. In CRISPR-Cas9 IgG2B KO, overexpression of factors involved in hematopoietic cells, neural stem cells and the regulation of neuritogenesis have been identified. Moreover, overexpression of IgG2B in astrocytes induces the CRTC1-CREB-BDNF signaling pathway known to be involved in gliogenesis whereas CRISPR-Cas9 IgG2B KO triggers the BMP/YAP1/TEAD3 pathway activated in astrocytes dedifferentiation into neural progenitors. Proximal labeling experiments revealed that IgG2B is N-glycosylated by the OST complex, addressed to vesicle membranes containing the ATPase complex; and behaves partially like CD98hc through its association with LAT1. Proximity-dependent biotin labeling experiments suggest that proximal IgG2B-LAT1 interaction occurs concomitantly with MACO-1 and C2CD2L, at the heart of a potentially novel cell signaling platform. Finally, we demonstrated that these chains are synthesized individually and associated to recognize specific targets. Indeed, intermediate filaments Eif4a2 and Pdia6 involved in astrocyte fate constitute targets for these neural IgGs. Taken together, we hypotheses that aberrant neural IgG chains may act as gatekeepers of astrocytes fate.

Dataset Information

Transcription profiling of rat neural progenitor cells and their differentiation into neurons and astrocytes

Publications

Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition.

Similar Datasets

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