TY - JOUR
T1 - Comparative RNA-seq Analysis in the Unsequenced Axolotl
T2 - The Oncogene Burst Highlights Early Gene Expression in the Blastema
AU - Stewart, Ron
AU - Rascón, Cynthia Alexander
AU - Tian, Shulan
AU - Nie, Jeff
AU - Barry, Chris
AU - Chu, Li Fang
AU - Ardalani, Hamisha
AU - Wagner, Ryan J.
AU - Probasco, Mitchell D.
AU - Bolin, Jennifer M.
AU - Leng, Ning
AU - Sengupta, Srikumar
AU - Volkmer, Michael
AU - Habermann, Bianca
AU - Tanaka, Elly M.
AU - Thomson, James A.
AU - Dewey, Colin N.
PY - 2013
Y1 - 2013
N2 - The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we performed deep RNA sequencing of the blastema over a time course in the axolotl, a species whose genome has not been sequenced. Using a novel comparative approach to analyzing RNA-seq data, we characterized the transcriptional dynamics of the regenerating axolotl limb with respect to the human gene set. This approach involved de novo assembly of axolotl transcripts, RNA-seq transcript quantification without a reference genome, and transformation of abundances from axolotl contigs to human genes. We found a prominent burst in oncogene expression during the first day and blastemal/limb bud genes peaking at 7 to 14 days. In addition, we found that limb patterning genes, SALL genes, and genes involved in angiogenesis, wound healing, defense/immunity, and bone development are enriched during blastema formation and development. Finally, we identified a category of genes with no prior literature support for limb regeneration that are candidates for further evaluation based on their expression pattern during the regenerative process.
AB - The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we performed deep RNA sequencing of the blastema over a time course in the axolotl, a species whose genome has not been sequenced. Using a novel comparative approach to analyzing RNA-seq data, we characterized the transcriptional dynamics of the regenerating axolotl limb with respect to the human gene set. This approach involved de novo assembly of axolotl transcripts, RNA-seq transcript quantification without a reference genome, and transformation of abundances from axolotl contigs to human genes. We found a prominent burst in oncogene expression during the first day and blastemal/limb bud genes peaking at 7 to 14 days. In addition, we found that limb patterning genes, SALL genes, and genes involved in angiogenesis, wound healing, defense/immunity, and bone development are enriched during blastema formation and development. Finally, we identified a category of genes with no prior literature support for limb regeneration that are candidates for further evaluation based on their expression pattern during the regenerative process.
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U2 - 10.1371/journal.pcbi.1002936
DO - 10.1371/journal.pcbi.1002936
M3 - Article
C2 - 23505351
AN - SCOPUS:84876007237
SN - 1553-734X
VL - 9
JO - PLoS computational biology
JF - PLoS computational biology
IS - 3
M1 - e1002936
ER -