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Cell Rep. 2017 Jan 17;18(3):762-776. doi: 10.1016/j.celrep.2016.12.063.

A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors.

Author information

1
Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women's Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA.
2
Broad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USA.
3
Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Sciences East, Stillwater, OK 74078, USA.
4
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
5
Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
6
Broad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: bhaas@broadinstitute.org.
7
Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women's Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA. Electronic address: jwhited@bwh.harvard.edu.

Abstract

Mammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-sequencing profiles for a broad spectrum of tissues that is estimated to have near-complete sequence information for 88% of axolotl genes. We devised expression analyses that identified the axolotl orthologs of cirbp and kazald1 as highly expressed and enriched in blastemas. Using morpholino anti-sense oligonucleotides, we find evidence that cirbp plays a cytoprotective role during limb regeneration whereas manipulation of kazald1 expression disrupts regeneration. Our transcriptome and annotation resources greatly complement previous transcriptomic studies and will be a valuable resource for future research in regenerative biology.

KEYWORDS:

Trinity; Trinotate; axolotl; blastema; cirbp; expression analysis; kazald1; limb; regeneration; transcriptome

PMID:
28099853
PMCID:
PMC5419050
DOI:
10.1016/j.celrep.2016.12.063
[Indexed for MEDLINE]
Free PMC Article

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