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Science. 2018 Oct 26;362(6413). pii: eaaq0681. doi: 10.1126/science.aaq0681. Epub 2018 Sep 27.

Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration.

Author information

1
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany.
2
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria. barbara_treutlein@eva.mpg.de elly.tanaka@imp.ac.at prayag.murawala@imp.ac.at.
3
Deutsche Forschungsgemeinschaft (DFG) Center for Regenerative Therapies (CRTD), Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany.
4
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria.
5
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. barbara_treutlein@eva.mpg.de elly.tanaka@imp.ac.at prayag.murawala@imp.ac.at.
6
Max Planck Institute of Molecular Cell Biology and Genetics, 108 Pfotenhauerstraße, 01307 Dresden, Germany.
7
Department of Biosciences, Technical University Munich, 85354 Freising, Germany.

Abstract

Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of blastema formation had previously been hampered by the inability to identify and isolate blastema precursor cells in the adult tissue. We have used a combination of Cre-loxP reporter lineage tracking and single-cell messenger RNA sequencing (scRNA-seq) to molecularly track mature connective tissue (CT) cell heterogeneity and its transition to a limb blastema state. We have uncovered a multiphasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that recapitulates an embryonic limb bud-like phenotype including multipotency within the CT lineage. Together, our data illuminate molecular and cellular reprogramming during complex organ regeneration in a vertebrate.

PMID:
30262634
DOI:
10.1126/science.aaq0681

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