Cerebral organoids display dynamic clonal growth and tunable tissue replenishment.

Autor: Lindenhofer D; Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria.; Vienna Biocenter PhD Program, University of Vienna and the Medical University of Vienna, Vienna, Austria.; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Haendeler S; Vienna Biocenter PhD Program, University of Vienna and the Medical University of Vienna, Vienna, Austria.; Center of Integrative Bioinformatics Vienna, Max Perutz Labs, University of Vienna and Medical University of Vienna, Vienna BioCenter, Vienna, Austria., Esk C; Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria. christopher.esk@uibk.ac.at.; Institute of Molecular Biology, University of Innsbruck, Innsbruck, Austria. christopher.esk@uibk.ac.at., Littleboy JB; Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria.; Vienna Biocenter PhD Program, University of Vienna and the Medical University of Vienna, Vienna, Austria., Brunet Avalos C; Institut Curie, PSL Research University, CNRS UMR144, Paris, France., Naas J; Vienna Biocenter PhD Program, University of Vienna and the Medical University of Vienna, Vienna, Austria.; Center of Integrative Bioinformatics Vienna, Max Perutz Labs, University of Vienna and Medical University of Vienna, Vienna BioCenter, Vienna, Austria., Pflug FG; Center of Integrative Bioinformatics Vienna, Max Perutz Labs, University of Vienna and Medical University of Vienna, Vienna BioCenter, Vienna, Austria.; Biological Complexity Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa, Japan., van de Ven EGP; Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria., Reumann D; Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria., Baffet AD; Institut Curie, PSL Research University, CNRS UMR144, Paris, France.; Institut national de la santé et de la recherche médicale, Paris, France., von Haeseler A; Vienna Biocenter PhD Program, University of Vienna and the Medical University of Vienna, Vienna, Austria.; Faculty of Computer Science, Bioinformatics and Computational Biology, University of Vienna, Vienna, Austria., Knoblich JA; Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria. juergen.knoblich@imba.oeaw.ac.at.; Department of Neurology, Medical University of Vienna, Vienna, Austria. juergen.knoblich@imba.oeaw.ac.at.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 May; Vol. 26 (5), pp. 710-718. Date of Electronic Publication: 2024 May 07.
DOI: 10.1038/s41556-024-01412-z
Abstrakt: During brain development, neural progenitors expand through symmetric divisions before giving rise to differentiating cell types via asymmetric divisions. Transition between those modes varies among individual neural stem cells, resulting in clones of different sizes. Imaging-based lineage tracing allows for lineage analysis at high cellular resolution but systematic approaches to analyse clonal behaviour of entire tissues are currently lacking. Here we implement whole-tissue lineage tracing by genomic DNA barcoding in 3D human cerebral organoids, to show that individual stem cell clones produce progeny on a vastly variable scale. By using stochastic modelling we find that variable lineage sizes arise because a subpopulation of lineages retains symmetrically dividing cells. We show that lineage sizes can adjust to tissue demands after growth perturbation via chemical ablation or genetic restriction of a subset of cells in chimeric organoids. Our data suggest that adaptive plasticity of stem cell populations ensures robustness of development in human brain organoids.
(© 2024. The Author(s).)
Databáze: MEDLINE
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