Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin.

Autor: Li X; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. xiaofei.li@ki.se., Andrusivova Z; Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden., Czarnewski P; Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.; Science for Life Laboratory, Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Stockholm University, Stockholm, Sweden., Langseth CM; Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden., Andersson A; Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.; Department of Artificial Intelligence and Machine Learning, Research and Early Development, Genentech. Inc., South San Francisco, CA, USA., Liu Y; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Gyllborg D; Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden., Braun E; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Larsson L; Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden., Hu L; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Alekseenko Z; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Lee H; Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden., Avenel C; Department of Information Technology, Uppsala University, Uppsala, Sweden.; BioImage Informatics Facility, Science for Life Laboratory, SciLifeLab, Sweden., Kallner HK; Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.; Department of Obstetrics and Gynecology, Danderyd Hospital, Danderyd, Sweden., Åkesson E; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; R&D Unit, Stockholms Sjukhem, Stockholm, Sweden., Adameyko I; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.; Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria., Nilsson M; Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden., Linnarsson S; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Lundeberg J; Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden., Sundström E; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. erik.sundstrom@ki.se.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2023 May; Vol. 26 (5), pp. 891-901. Date of Electronic Publication: 2023 Apr 24.
DOI: 10.1038/s41593-023-01312-9
Abstrakt: The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5-12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.
(© 2023. The Author(s).)
Databáze: MEDLINE
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