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NOCICEPTRA: Gene and microRNA signatures and their trajectories characterizing human iPSC-derived nociceptor maturation

ABSTRACT: NOCICEPTRA: Gene and microRNA signatures and their trajectories characterizing human iPSC-derived nociceptor maturation

PROVIDER: PRJNA678653 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13066200.fastq.gz	Fastqsanger.gz
	SRR13066201.fastq.gz	Fastqsanger.gz
	SRR13066202.fastq.gz	Fastqsanger.gz
	SRR13066203.fastq.gz	Fastqsanger.gz
	SRR13066204.fastq.gz	Fastqsanger.gz

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NOCICEPTRA: Gene and microRNA signatures and their trajectories characterizing human iPSC-derived nociceptor maturation

Project description:Nociceptors are specialized sensory neurons implicated in the reception and transduction of painful stimuli. Many pain disorders directly affect nociceptors but mechanistic insight into underlying pathway regulations is limited by the translational paresis from animal models to human pain disorders. Although transcriptomic data are available for rodent and post-mortem patient samples, no comprehensive transcriptomic data are currently available for human nociceptor development. Here, we performed paired long and small RNA sequencing for six timepoints during nociceptor differentiation from three different human iPSC cell lines. Complex bioinformatics analyses for differential gene expression, protein-protein interactions and mRNA targeting by microRNAs revealed five distinct differentiation stages with critical hub genes and microRNAs guiding nociceptor development. The online resource platform NOCICEPTRA was specifically developed to visualize respective mRNA and microRNA trajectories, as well as query disease specific pathways, thereby enabling researchers to determine susceptibility windows for nociceptor-associated disorders as well as possible new treatment targets.

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NOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC-Derived Nociceptor Maturation.

Project description:Nociceptors are primary afferent neurons serving the reception of acute pain but also the transit into maladaptive pain disorders. Since native human nociceptors are hardly available for mechanistic functional research, and rodent models do not necessarily mirror human pathologies in all aspects, human induced pluripotent stem cell-derived nociceptors (iDN) offer superior advantages as a human model system. Unbiased mRNA::microRNA co-sequencing, immunofluorescence staining, and qPCR validations, reveal expression trajectories as well as miRNA target spaces throughout the transition of pluripotent cells into iDNs. mRNA and miRNA candidates emerge as regulatory hubs for neurite outgrowth, synapse development, and ion channel expression. The exploratory data analysis tool NOCICEPTRA is provided as a containerized platform to retrieve experimentally determined expression trajectories, and to query custom gene sets for pathway and disease enrichments. Querying NOCICEPTRA for marker genes of cortical neurogenesis reveals distinct similarities and differences for cortical and peripheral neurons. The platform provides a public domain neuroresource to exploit the entire data sets and explore miRNA and mRNA as hubs regulating human nociceptor differentiation and function.

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Advanced iPSC-CMs maturation by integrating maturation medium, nanopatterning, and electrical stimulation

Project description:The generation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offers an unlimited source of patient-specific human cardiomyocytes. However, the use of iPSC-CM in vitro-models to guide the clinic selection of particular drugs for individual patients remains a vision. A major limitation represents the immature phenotype of iPSC-CMs, which alters their sensitivity towards physiological and pathophysiological stimuli, cardioactive drugs or toxic substances, in comparison to adult cardiomyocytes (CMs). In this study, we aim to generate iPSC-CMs with an advanced maturation state by combining the use of MM with the alignment of the cells on nanopatterned surfaces (NP) and induction of an increased contractile workload by electrical stimulation (ES). Under the combined influence of MM, NP and ES, iPSC-CMs develop a more complex cellular structure, increased mitochondrial content and enhanced electrophysiological properties. Furthermore, the response of iPSC-CMs matured under influence of MM, NP and ES to isoprenaline as well as verapamil differs to less mature iPSC-CMs cultured in B27-medium. Taken together, our results reveal that the combination of MM, NP and ES strongly improves the maturation state of iPSC-CMs and that this advanced maturation state critically affects the cell behavior in functional studies as well as response to cardioactive drugs.

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