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

Leigh, Nicholas D LU orcid ; Dunlap, Garrett S ; Johnson, Kimberly ; Mariano, Rachelle ; Oshiro, Rachel ; Wong, Alan Y ; Bryant, Donald M ; Miller, Bess M ; Ratner, Alex and Chen, Andy , et al. (2018) In Nature Communications 9.
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ambystoma mexicanum/genetics, Animal Experimentation, Animals, Cell Differentiation, Cell Lineage, Epidermal Cells, Epidermis/pathology, Extremities/embryology, Fibroblasts/cytology, Gene Expression Profiling, Gene Expression Regulation, Developmental/genetics, Immune System/physiology, In Situ Hybridization, Macrophages, Mesenchymal Stem Cells, Myeloid Cells/physiology, Nerve Regeneration/physiology, Neurons/physiology, Regeneration/genetics, Sequence Analysis, RNA, Stem Cells/cytology, Transcriptome
in
Nature Communications
volume
9
article number
5153
publisher
Nature Publishing Group
external identifiers
  • pmid:30514844
  • scopus:85057600354
ISSN
2041-1723
DOI
10.1038/s41467-018-07604-0
language
English
LU publication?
no
id
9757d13b-b064-4dce-a61a-27b2ce5feb9f
date added to LUP
2020-04-27 20:52:13
date last changed
2024-07-10 15:26:10
@article{9757d13b-b064-4dce-a61a-27b2ce5feb9f,
  abstract     = {{<p>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.</p>}},
  author       = {{Leigh, Nicholas D and Dunlap, Garrett S and Johnson, Kimberly and Mariano, Rachelle and Oshiro, Rachel and Wong, Alan Y and Bryant, Donald M and Miller, Bess M and Ratner, Alex and Chen, Andy and Ye, William W and Haas, Brian J and Whited, Jessica L}},
  issn         = {{2041-1723}},
  keywords     = {{Ambystoma mexicanum/genetics; Animal Experimentation; Animals; Cell Differentiation; Cell Lineage; Epidermal Cells; Epidermis/pathology; Extremities/embryology; Fibroblasts/cytology; Gene Expression Profiling; Gene Expression Regulation, Developmental/genetics; Immune System/physiology; In Situ Hybridization; Macrophages; Mesenchymal Stem Cells; Myeloid Cells/physiology; Nerve Regeneration/physiology; Neurons/physiology; Regeneration/genetics; Sequence Analysis, RNA; Stem Cells/cytology; Transcriptome}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution}},
  url          = {{http://dx.doi.org/10.1038/s41467-018-07604-0}},
  doi          = {{10.1038/s41467-018-07604-0}},
  volume       = {{9}},
  year         = {{2018}},
}