Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution

Nicholas D. Leigh, Garrett S. Dunlap, Kimberly Johnson, Rachelle Mariano, Rachel Oshiro, Alan Y. Wong, Donald M. Bryant, Bess M. Miller, Alex Ratner, Andy Chen, William W. Ye, Brian J. Haas and Jessica L. Whited ()
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Nicholas D. Leigh: Brigham and Women’s Hospital
Garrett S. Dunlap: Brigham and Women’s Hospital
Kimberly Johnson: Brigham and Women’s Hospital
Rachelle Mariano: Brigham and Women’s Hospital
Rachel Oshiro: Brigham and Women’s Hospital
Alan Y. Wong: Brigham and Women’s Hospital
Donald M. Bryant: Brigham and Women’s Hospital
Bess M. Miller: Brigham and Women’s Hospital
Alex Ratner: Harvard Medical School
Andy Chen: Brigham and Women’s Hospital
William W. Ye: Brigham and Women’s Hospital
Brian J. Haas: Broad Institute of MIT and Harvard
Jessica L. Whited: Brigham and Women’s Hospital

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, defining the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. Here we report unbiased single-cell RNA-sequencing on over 25,000 cells from axolotl limbs and identify a plethora of cellular diversity within epidermal, mesenchymal, and hematopoietic lineages in homeostatic and regenerating limbs. We identify regeneration-induced genes, develop putative trajectories for blastema cell differentiation, and propose the molecular identity of fibroblast-like blastema progenitor cells. This work will enable application of molecular techniques to assess the contribution of these populations to limb regeneration. Overall, these data allow for establishment of a putative framework for adult axolotl limb regeneration.

Date: 2018
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DOI: 10.1038/s41467-018-07604-0

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