This scRNA-seq experiment is an integral part of a manuscript with the above title. Our analysis of the scRNA-seq data suggests that activated CARD11 promotes immunoglobulin class-switching in germinal center B cells and generation of IgG1-secreting plasma cells. Overall design: Single-cell suspensions were prepared from spleens harvested from mice 5 days post immunization with sheep red blood cells. B cells were enriched using an immunomagnetic negative selection kit. scRNA-seq was performed using the Chromium product suite by 10x Genomics.
Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation.
Cell line, Subject
View SamplesNeurospheres generated in vitro were treated with non-epinephrine or potassium chloride. Gene expression analysis was then carried out to identify genes that are up or down regulated due to chemical treatement.
A comparative study of techniques for differential expression analysis on RNA-Seq data.
Sex, Specimen part
View SamplesMyelination is essential for nervous system function. Schwann cells interact with neurons and with the basal lamina to sort and myelinate axons, using known receptors and signaling pathways. In contrast, the transcriptional control of axonal sorting and the role of mechano-transduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. Here, we describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice we show that Taz is required in Schwann cells for radial sorting and myelination. Yap is redundant with Taz as ablation of both Yap and Taz abolishes radial sorting. Yap/Taz regulate Schwann cell proliferation and transcription of basal lamina receptors, both necessary for proper radial sorting of axons, and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells. Overall design: 3 cKO and 3 control wild-type mice
YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Specimen part, Treatment
View SamplesThe development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Treatment
View SamplesThe development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Specimen part, Treatment
View SamplesHippo signalling has been implicated as a key regulator of tissue regeneration. In the intestine, ex vivo organoid cultures model aspects of crypt epithelial regeneration. Therefore in order to uncover the Yap regulated transcriptional programs during crypt regeneration we performed RNA-sequencing of Yap wt and Yap deficient organoids, as well as organoids inducibly expressing Yap. Overall design: Yap loss of function organoids were harvested from Yapfl/fl;VillinCre mice (Yap-/-). In addition, we developed Yap overexpressing organoids by generating a doxycycline-inducible wild-type Yap transgenic line under the control of a Cre driven reverse tetracycline transactivator (rtTA), referred to here as YapTg. Organoids were seeded on day 0 from whole crypts isolated from Yap+/D, YapD/D, YapTg mice and cultured for 24 hours at which time they were harvested for transcriptome analysis by RNAseq.
Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer.
No sample metadata fields
View SamplesThe hypothesis is that genes involved in the immature schwann cell and promyelinating state will be upregulated and genes that are involved in the myelnating state will be down regulated.
MicroRNA-deficient Schwann cells display congenital hypomyelination.
Sex, Specimen part
View SamplesComparison of gene expresion profile of 4 SC clones and 4 SI clones at different time points defined a stabilization competency signiture required for successful reprogramming Overall design: mRNA profilling 4 SI clones at 5 time points, 4 SC clones at 6 time points, and 3 feeder samples.
A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network.
Specimen part, Subject
View SamplesWe have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves.
Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.
Age, Specimen part
View Samples