A multi-omics approach to visualize early neuronal differentiation from hESCs in 4D
Athina Samara,
Mari Spildrejorde,
Ankush Sharma,
Martin Falck,
Magnus Leithaug,
Stefania Modafferi,
Pål Marius Bjørnstad,
Ganesh Acharya,
Kristina Gervin,
Robert Lyle,
Ragnhild Eskeland
Affiliations
Athina Samara
Division of Clinical Paediatrics, Department of Women’s and Children’s Health, Karolinska Institutet, Solna, Sweden; Astrid Lindgren Children′s Hospital Karolinska University Hospital, Stockholm, Sweden; Corresponding author
Mari Spildrejorde
PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Ankush Sharma
Department of Informatics, University of Oslo, Oslo, Norway; Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway
Martin Falck
PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway
Magnus Leithaug
Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
Stefania Modafferi
Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
Pål Marius Bjørnstad
Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
Ganesh Acharya
Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Alfred Nobels Allé 8, SE-14152 Stockholm, Sweden; Center for Fetal Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Kristina Gervin
PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, School of Pharmacy, University of Oslo, Oslo, Norway; Division of Clinical Neuroscience, Department of Research and Innovation, Oslo University Hospital, Oslo, Norway
Robert Lyle
PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Corresponding author
Ragnhild Eskeland
PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Corresponding author
Summary: Neuronal differentiation of pluripotent stem cells is an established method to study physiology, disease, and medication safety. However, the sequence of events in human neuronal differentiation and the ability of in vitro models to recapitulate early brain development are poorly understood. We developed a protocol optimized for the study of early human brain development and neuropharmacological applications. We comprehensively characterized gene expression and epigenetic profiles at four timepoints, because the cells differentiate from embryonic stem cells towards a heterogeneous population of progenitors, immature and mature neurons bearing telencephalic signatures. A multi-omics roadmap of neuronal differentiation, combined with searchable interactive gene analysis tools, allows for extensive exploration of early neuronal development and the effect of medications.
