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

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 stu...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2017-01-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716317703
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author 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
spellingShingle 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
A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
Cell Reports
axolotl
transcriptome
Trinity
Trinotate
limb
regeneration
blastema
expression analysis
cirbp
kazald1
author_facet 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
author_sort Donald M. Bryant
title A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
title_short A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
title_full A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
title_fullStr A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
title_full_unstemmed A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors
title_sort tissue-mapped axolotl de novo transcriptome enables identification of limb regeneration factors
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2017-01-01
description 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.
topic axolotl
transcriptome
Trinity
Trinotate
limb
regeneration
blastema
expression analysis
cirbp
kazald1
url http://www.sciencedirect.com/science/article/pii/S2211124716317703
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spelling doaj-1952cf1abfac437ca3a57a2785b1e5782020-11-25T01:32:29ZengElsevierCell Reports2211-12472017-01-0118376277610.1016/j.celrep.2016.12.063A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration FactorsDonald M. Bryant0Kimberly Johnson1Tia DiTommaso2Timothy Tickle3Matthew Brian Couger4Duygu Payzin-Dogru5Tae J. Lee6Nicholas D. Leigh7Tzu-Hsing Kuo8Francis G. Davis9Joel Bateman10Sevara Bryant11Anna R. Guzikowski12Stephanie L. Tsai13Steven Coyne14William W. Ye15Robert M. Freeman Jr.16Leonid Peshkin17Clifford J. Tabin18Aviv Regev19Brian J. Haas20Jessica L. Whited21Harvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USABroad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USADepartment of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Sciences East, Stillwater, OK 74078, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USADepartment of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USADepartment of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USADepartment of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USADepartment of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USABroad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USABroad Institute of MIT and Harvard and Klarman Cell Observatory, 7 Cambridge Center, Cambridge, MA 02142, USAHarvard Medical School, Harvard Stem Cell Institute, and Department of Orthopedic Surgery, Brigham & Women’s Hospital, 65 Landsdowne St., Cambridge, MA 02139, USAMammals 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.http://www.sciencedirect.com/science/article/pii/S2211124716317703axolotltranscriptomeTrinityTrinotatelimbregenerationblastemaexpression analysiscirbpkazald1