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.

Details

Title
Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution
Author
Leigh, Nicholas D 1 ; Dunlap, Garrett S 1   VIAFID ORCID Logo  ; Johnson, Kimberly 1   VIAFID ORCID Logo  ; Mariano, Rachelle 2 ; Oshiro, Rachel 2 ; Wong, Alan Y 3   VIAFID ORCID Logo  ; Bryant, Donald M 2 ; Miller, Bess M 1 ; Ratner, Alex 4 ; Chen, Andy 2 ; Ye, William W 2 ; Haas, Brian J 5 ; Whited, Jessica L 6 

1  Department of Orthopedic Surgery, Harvard Medical School, The Harvard Stem Cell Institute, Brigham and Women’s Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA 
2  Department of Orthopedic Surgery, Harvard Medical School, The Harvard Stem Cell Institute, Brigham and Women’s Hospital, Boston, MA, USA 
3  Department of Orthopedic Surgery, Harvard Medical School, The Harvard Stem Cell Institute, Brigham and Women’s Hospital, Boston, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA 
4  ICCB-L Single Cell Core, Harvard Medical School, Boston, MA, USA 
5  Broad Institute of MIT and Harvard, Cambridge, MA, USA 
6  Department of Orthopedic Surgery, Harvard Medical School, The Harvard Stem Cell Institute, Brigham and Women’s Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA 
Pages
1-14
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-07604-0
ProQuest document ID
2149889108
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.