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

Tobias Gerber, Prayag Murawala, Dunja Knapp, Wouter Masselink, Maritta Schuez, Sarah Hermann, Malgorzata Gac-Santel, Sergej Nowoshilow, Jorge Kageyama, Shahryar Khattak, Joshua D. Currie, J. Gray Camp, Elly M. Tanaka, Barbara Treutlein

Research output: Contribution to journalArticlepeer-review

222 Scopus citations

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.

Original languageEnglish
Article numbereaaq0681
JournalScience
Volume362
Issue number6413
DOIs
StatePublished - 26 Oct 2018

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