Cell Reports (Jan 2017)
A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
- Donald M. Bryant,
- Kimberly Johnson,
- Tia DiTommaso,
- Timothy Tickle,
- Matthew Brian Couger,
- Duygu Payzin-Dogru,
- Tae J. Lee,
- Nicholas D. Leigh,
- Tzu-Hsing Kuo,
- Francis G. Davis,
- Joel Bateman,
- Sevara Bryant,
- Anna R. Guzikowski,
- Stephanie L. Tsai,
- Steven Coyne,
- William W. Ye,
- Robert M. Freeman Jr.,
- Leonid Peshkin,
- Clifford J. Tabin,
- Aviv Regev,
- Brian J. Haas,
- Jessica L. Whited
Affiliations
- Donald M. Bryant
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Kimberly Johnson
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Tia DiTommaso
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Timothy Tickle
- Broad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USA
- Matthew Brian Couger
- Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Sciences East, Stillwater, OK 74078, USA
- Duygu Payzin-Dogru
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Tae J. Lee
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Nicholas D. Leigh
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Tzu-Hsing Kuo
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Francis G. Davis
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Joel Bateman
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Sevara Bryant
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Anna R. Guzikowski
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Stephanie L. Tsai
- Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
- Steven Coyne
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- William W. Ye
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- Robert M. Freeman Jr.
- Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
- Leonid Peshkin
- Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
- Clifford J. Tabin
- Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
- Aviv Regev
- Broad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USA
- Brian J. Haas
- Broad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USA
- Jessica L. Whited
- Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA
- DOI
- https://doi.org/10.1016/j.celrep.2016.12.063
- Journal volume & issue
-
Vol. 18,
no. 3
pp. 762 – 776
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
- axolotl
- transcriptome
- Trinity
- Trinotate
- limb
- regeneration
- blastema
- expression analysis
- cirbp
- kazald1
