It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitro. To study the molecular profile of these NSCs in detail, we performed RNA sequencing and mass spectrometry on CD271+ NSCs isolated from human post-mortem SVZ and on homogenates of the SVZ. CD271+ cells were isolated through magnetic cell separation (MACS). We first compared the molecular profile of CD271+ NSCs to the SVZ homogenate from control donors to assess the CD271+ NSCs gene signature and finally made a comparison between controls and PD patients to establish a specific molecular profile of NSCs and the SVZ in PD. While our transcriptome analysis did not identify any differentially expressed genes in the SVZ between control and PD patients, our proteome analysis revealed several proteins that were differentially expressed in PD. Some of these proteins are involved in cytoskeletal organization and mitochondrial function. Transcriptome and proteome analyses of NSCs from PD revealed changes in the expression of genes and proteins involved in metabolism, transcriptional activity and cytoskeletal organization. Our results not only confirm pathological hallmarks of PD (e.g. impaired mitochondrial function), but also suggest that NSCs may transit into a primed-quiescent state, that is in an “alert” non-proliferative phase in PD. Overall design: From post-mortem human SVZ of control and Parkinson disease donors we isolated CD271+ NSCs and Cd11b+ microglia by MACS and the whole SVZ to generate RNA sequencing libraries using Celseq2 method. We aimed for low coverage sequencing (~2 million mapped to the coding regions) per sample to investigate the gross changes in the transcriptome. Libraries (rpi small primer) were sequenced in 3 runs, 2 on an Illumina NextSeq500 using 75-bp paired-end sequencing at the Utrecht Seuqencing center (USEQ) and the third on a HiSeq4000 using 150-bp paired-end sequencing at Genomescan. All the samples were mapped in a single run to an average depth of ~10 million reads per sample. Reads were mapped to the latest human coding transcriptome using bwa, normalized and analyzed using the standard DESEQ2 package.
Transcriptome and proteome profiling of neural stem cells from the human subventricular zone in Parkinson's disease.
Specimen part, Subject
View SamplesHuman dendritic cells were exposed to LPS, in the absence and presence of adenosine receptor 3 inhibitor Overall design: 4 donors, 4 experimental conditions. VUF concentration used was 5 µM, LPS was 500 ng/ml. Exposure times were 6 hours
TLR-Induced IL-12 and CCL2 Production by Myeloid Cells Is Dependent on Adenosine A<sub>3</sub> Receptor-Mediated Signaling.
Specimen part, Subject
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Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation.
Subject, Time
View SamplesHealthy human adults were recruited to a sleep lab at Washington State University and remained there 7 consecutive days. Six received a well-rested Control condition of 10 h Time-In-Bed (TIB) nightly.
Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation.
Subject, Time
View SamplesHealthy human adults were recruited to a sleep lab at Washington State University and remained there 7 consecutive days. Six received a well-rested Control condition of 10 h Time-In-Bed (TIB) nightly.
Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation.
Subject, Time
View SamplesHealthy human adults were recruited to a sleep lab at Washington State University and remained there 7 consecutive days. Six received a well-rested Control condition of 10 h Time-In-Bed (TIB) nightly.
Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation.
Subject, Time
View SamplesOrganoid technology provides the possibility to culture human colon tissue and patient-derived colorectal cancers (CRC) while maintaining all functional and phenotypic characteristics. Labeling of human colon stem cells (CoSCs), especially in normal and benign tumor organoids, is challenging and therefore limits usability of multi-patient organoid libraries for CoSC research. Here, we developed STAR (STem cell Ascl2 Reporter), a minimal enhancer/promoter element that reports transcriptional activity of ASCL2, a master regulator of LGR5+ CoSC fate. Among others via lentiviral infection, STAR minigene labels stem cells in normal as well as in multiple engineered and patient-derived CRC organoids of different stage and genetic make-up. STAR revealed that stem cell driven differentiation hierarchies and the capacity of cell fate plasticity (de-differentiation) are present at all stages of human CRC development. The flexible and user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research on human adult stem cell biology. Overall design: Cells from different colon organoid types were FACS sorted for stem STemness Ascl2 Reporter activity for transcriptome profiling by RNA-seq.
Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene.
Subject
View SamplesDrosophila neuroblasts have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type specific gene expression data. Here, we describe a methodology to isolate large numbers of pure neuroblasts and differentiating neurons that retain both cell cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted neuroblast specific transcription factors, which can be arranged in a network containing hubs for Notch signaling, growth control and chromatin regulation. Overexpression and RNAi for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klu function causes premature differentiation while overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for Drosophila developmental neurobiology and we describes methodology that can be applied to other invertebrate stem cell lineages as well. Overall design: comparison of transcriptomes of Drosophila melanogaster larval neuroblasts and their differentiated daughter cells (neurons)
FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal.
Specimen part, Subject
View SamplesTitle: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA.
Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.
No sample metadata fields
View SamplesGene expression profiles in Ba/F3 cells expressing ETV6-PDGFRB, FIP1L1-PDGFRA or a control vector, treated or not with imatinib (Glivec)
The expression of the tumour suppressor HBP1 is down-regulated by growth factors via the PI3K/PKB/FOXO pathway.
Specimen part, Cell line, Treatment
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