Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MicroRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis

ABSTRACT: MicroRNAs (miRNAs) are short (~22 nt) single-stranded non-coding RNAs that regulate gene expression at the post-transcriptional level. Over the past years, many studies have extensively characterized the involvement of miRNA-mediated regulation in neurogenesis and brain development. However, a comprehensive catalog of cortical miRNAs cell-specifically expressed in progenitor types of the developing mammalian cortex is still missing. Overcoming this limitation, here we exploited a double reporter mouse line previously validated by our group to allow the identification of the transcriptional signature to neurogenic commitment and provide the field with the complete atlas of miRNAs expression in proliferating neural stem cells, neurogenic progenitors and newborn neurons during corticogenesis. By extending the currently known list of miRNAs expressed in the mouse brain by over two fold, our study highlights the power of cell type-specific analyses for the detection of transcripts that would otherwise be diluted out when studying bulk tissues. We further exploited our data by predicting putative novel miRNAs and validated the power of our approach by providing novel evidence for the involvement of miR-486 as a novel player in brain development.

ORGANISM(S): Mus musculus

PROVIDER: GSE142253 | GEO | 2020/04/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome Sequencing During Mouse Brain Development Identifies Long Non-Coding RNAs Functionally Involved in Neurogenic Commitment

Project description:Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem cell commitment during neurogenesis. M-bM-^@M-^\LncRNAs control neurogenesisM-bM-^@M-^] Aprea, Prenninger, Dori, Monasor, Wessendof, Zocher, Massalini, Ghosh, Alexopoulou, Lesche, Dahl, Groszer, Hiller, Calegari, The EMBO Journal (In Press) mRNA profiles of Proliferating Progenitors, Differentiating Progenitors and Neurons from lateral cortex of E14.5 mouse embryos. Each cell type in three biological replicates.

2013-11-18 | E-GEOD-51606 | biostudies-arrayexpress

Transcriptome Sequencing During Mouse Brain Development Identifies Long Non-Coding RNAs Functionally Involved in Neurogenic Commitment

Project description:Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem cell commitment during neurogenesis. “LncRNAs control neurogenesis” Aprea, Prenninger, Dori, Monasor, Wessendof, Zocher, Massalini, Ghosh, Alexopoulou, Lesche, Dahl, Groszer, Hiller, Calegari, The EMBO Journal (In Press)

2013-11-18 | GSE51606 | GEO

Novel primate miRNAs co-evolved with ancient target genes in germinal zone specific expression patterns [miRNA-Seq]

Project description:Major non primate-primate differences in corticogenesis include the dimensions, precursor lineages and developmental timing of the germinal zones (GZ). microRNAs (miRNAs) of laser dissected GZ compartments and cortical plate (CP) from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ including Ventricular Zone (VZ), outer and inner subcompartments of the Outer SubVentricular Zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs present in primate, but absent in rodent, contributed disproportionately to the differential expression between GZ sub-regions. Prominent among the validated targets of these miRNAs were cell-cycle and neurogenesis regulators. Co-evolution between the emergent miRNAs and their targets suggested that novel miRNAs became integrated into ancient gene circuitry to exert additional control over proliferation. We conclude that multiple cell-cycle regulatory events contribute to the emergence of primate-specific cortical features, including the OSVZ, generated enlarged supragranular layers, largely responsible for the increased primate cortex computational abilities. Seven brain regions (VZ17, OSVZ17int, OSVZ17ext, CP17, VZ18, OSVZ18, CP18). OSVZ17int corresponds to the inner (apical) third of OSVZ 17 and OSVZ17ext to the most outer (basal) third of OSVZ 17, located immediately below the Outer Fiber Layer (Smart et al., 2002; Betizeau et al., 2013)

2014-02-27 | E-GEOD-52606 | biostudies-arrayexpress

Novel primate miRNAs co-evolved with ancient target genes in germinal zone specific expression patterns [RISC trap immunoprecipitation]

Project description:Major non primate-primate differences in corticogenesis include the dimensions, precursor lineages and developmental timing of the germinal zones (GZ). microRNAs (miRNAs) of laser dissected GZ compartments and cortical plate (CP) from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ including Ventricular Zone (VZ), outer and inner subcompartments of the Outer SubVentricular Zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs present in primate, but absent in rodent, contributed disproportionately to the differential expression between GZ sub-regions. Prominent among the validated targets of these miRNAs were cell-cycle and neurogenesis regulators. Co-evolution between the emergent miRNAs and their targets suggested that novel miRNAs became integrated into ancient gene circuitry to exert additional control over proliferation. We conclude that multiple cell-cycle regulatory events contribute to the emergence of primate-specific cortical features, including the OSVZ, generated enlarged supragranular layers, largely responsible for the increased primate cortex computational abilities. target mRNAs for selected miRNAs were detected with RISC trap immunoprecipitation

2014-02-27 | E-GEOD-52607 | biostudies-arrayexpress

Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

Project description:MicroRNAs (miRNAs) are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5) mouse brain. We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. We also discovered 4 putative 22-23nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099. We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099, with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development. Deep sequencing analysis of small RNAs isolated from an E15.5 mouse brain.

2011-04-04 | E-GEOD-22653 | biostudies-arrayexpress

TLS-CHOP Fusion Oncoprotein Regulates MicroRNA-486 in Human Myxoid Liposarcoma

Project description:MicroRNAs (miRNAs, miRs) are small noncoding RNAs, which control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumor suppressor genes, play important roles in carcinogenesis. Myxoid liposarcomas (MLS) are characterized by t(12;16)(q13;p11) translocation and expression of TLS/CHOP chimeric transcripts (various types) which encode different oncogenic proteins. TLS-CHOP is important for the molecular mechanisms in the development of MLS, but the involvement in microRNA expression still remain poorly understood. Thus we explored the target microRNA of TLS-CHOP influence cell-proliferation or cell death with microarray. MicroRNAs (miRNAs, miRs) are small noncoding RNAs, which control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumor suppressor genes, play important roles in carcinogenesis. Myxoid liposarcomas (MLS) are characterized by t(12;16)(q13;p11) translocation and expression of TLS/CHOP chimeric transcripts (various types) which encode different oncogenic proteins. TLS-CHOP is important for the molecular mechanisms in the development of MLS, but the involvement in microRNA expression still remain poorly understood. In this study, we have found that miR-486-5p (miR-486) expression level was downregulated by ectopic expression of TLS-CHOP fusion gene in mouse fibroblast cells (NIH3T3). In addition, we found overexpression of miR-486 inhibited the cell growth in the 2645/94 cells and in situ hybridization of miR-486 showed MLS tissues had lower signal intensity compared with non-tumor tissues. Thus we explored the target genes of miR-486 influence cell-proliferation or cell death with microarray. We compared the microRNA profiles of cells treated with TLS-CHOP or empty vector about NIH-3T3 cell-line. We compared the whole mRNA profiles of cells transfected with miR-486 oligonucleotides or control oligo about myxoid liposarcoma cell-line.

2013-03-23 | E-GEOD-36966 | biostudies-arrayexpress

Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

2011-04-05 | GSE22653 | GEO

Benchmarking brain organoid recapitulation of fetal corticogenesis

Project description:Brain organoids (BO) enabled the investigation of human corticogenesis in-vitro with an increasing range of protocols achieving its remarkable recapitulation. However, we lack a resource gathering fetal cortex-specific gene co-expression patterns and their behavior in BO. We complement the current knowledge with a benchmarking of BO versus human corticogenesis, integrating: transcriptomes from in-house differentiated cortical BO (CBO), in-house processed human fetal brain samples, analysis of transcriptomes from different BO systems and of pre-natal cortical samples from the BrainSpan Atlas.

2022-12-31 | E-MTAB-11239 | biostudies-arrayexpress