Mapping origins of variation in neural trajectories of human pluripotent stem cells
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ABSTRACT:
PROVIDER: PRJNA688712 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13331100_1.fastq.gz | Fastqsanger.gz | |||
| SRR13331100_2.fastq.gz | Fastqsanger.gz | |||
| SRR13331200_1.fastq.gz | Fastqsanger.gz | |||
| SRR13331200_2.fastq.gz | Fastqsanger.gz | |||
| SRR13331101_1.fastq.gz | Fastqsanger.gz |
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Project description:Mapping origins of variation in neural trajectories of human pluripotent stem cells [SOX21 KO RNA-seq]
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Project description:Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. We identify differences in the spontaneous self-organization of individual hPSC lines during self-renewal that lie along a fundamental axis of in vivo development. Distinct stable and dynamic transcriptional elements were revealed by decomposition of RNA-seq data in pluripotency and early lineage emergence. Stable differences within pluripotency predicted regional bias in the dynamics of neural differentiation that were also observed in large collections of hPSC lines. Using replicate human induced PSC (hiPSC) lines and paired adult tissue, we demonstrate that cells from individual humans expressed unique transcriptional signatures that were maintained throughout life. In addition, replicate hiPSC lines from one donor showed divergent expression phenotypes driven by distinct chromatin states. These stable transcriptional states are under both genetic and epigenetic control and predict bias in subsequent forebrain and hindbrain neural trajectories. These results define mechanisms controlling transcription in pluripotency to first establish human neural diversity.
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Project description:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease. Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors, early neurons, and brain organoids. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis. Multiple dysregulated proteins were found in pathways related to synapses, in line with postmortem tissue studies of schizophrenia patients. However, organoids and immature neurons exhibit impairments in pathways never before found in patient-derived induced pluripotent stem cell studies, such as spliceosomes and amino acid metabolism. In conclusion, here we provide comprehensive, large-scale, protein-level data that may uncover underlying mechanisms of the developmental origins of schizophrenia.
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Project description:Skin-derived precursors (SKPs) are multipotent dermal stem cells that reside within a hair follicle niche and that share properties with embryonic neural crest precursors. Here, we have asked whether SKPs and their endogenous dermal precursors originate from the neural crest or whether, like the dermis itself, they originate from multiple developmental origins. To do this, we used two different mouse Cre lines that allow us to perform lineage tracing: Wnt1-cre, which targets cells deriving from the neural crest, and Myf5-cre, which targets cells of a somite origin. By crossing these Cre lines to reporter mice, we show that the endogenous follicle-associated dermal precursors in the face derive from the neural crest, and those in the dorsal trunk derive from the somites, as do the SKPs they generate. In spite of these different developmental origins, SKPs from these two locations are functionally similar, even with regard to their ability to differentiate into Schwann cells, a cell type only thought to be generated from the neural crest. Analysis of global gene expression using microarrays confirmed that facial and dorsal SKPs exhibit a very high degree of similarity, and that they are also very similar to SKPs derived from ventral dermis, which has a lateral plate origin. However, these developmentally-distinct SKPs also retain differential expression of a small number of genes that reflect their developmental origins. Thus, an adult neural crest-like dermal precursor can be generated from a non-neural crest origin, a finding with broad implications for the many neuroendocrine cells in the body. We obtained three independent isolates each of dorsal trunk SKPs, ventral trunk SKPs and facial SKPs and four isolates of MSCs, all generated from adult rats. RNA samples deriving from these cells were analyzed on the Affymetrix GeneChip Rat Gene 1.0 ST Array.
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Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5M-bM-^@M-^Y half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes. This SuperSeries is composed of the following subset Series: GSE21781: Mapping origins of replication in Arabidopsis thaliana: Examination of BrdU labelled DNA and unlabelled DNA in one cell type GSE21827: Mapping origins of replication in Arabidopsis thaliana: H3K4ac ChIP vs. unmodified H3 ChIP Refer to individual Series
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