title: In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing.
abstract: Traumatic lower-limb musculoskeletal injuries are pervasive amongst athletes and the military and typically an individual returns to activity prior to fully healing, increasing a predisposition for additional injuries and chronic pain. Monitoring healing progression after a musculoskeletal injury typically involves different types of imaging but these approaches suffer from several disadvantages. Isolating and profiling transcripts from the injured site would abrogate these shortcomings and provide enumerative insights into the regenerative potential of an individual's muscle after injury. In this study, a traumatic injury was administered to a mouse model and healing progression was examined from 3 hours to 1 month using high-throughput RNA-Sequencing (RNA-Seq). Comprehensive dissection of the genome-wide datasets revealed the injured site to be a dynamic, heterogeneous environment composed of multiple cell types and thousands of genes undergoing significant expression changes in highly regulated networks. Four independent approaches were used to determine the set of genes, isoforms, and genetic pathways most characteristic of different time points post-injury and two novel approaches were developed to classify injured tissues at different time points. These results highlight the possibility to quantitatively track healing progression in situ via transcript profiling using high- throughput sequencing.
authors.affiliation: Massachusetts Institute of Technology - Lincoln Laboratory, Lexington, MA 02127, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar
authors.affiliation: Massachusetts Institute of Technology - Lincoln Laboratory, Lexington, MA 02127, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Shcherbina
authors.affiliation: Massachusetts Institute of Technology - Lincoln Laboratory, Lexington, MA 02127, USA.
authors.forename: Darrell O
authors.initials: DO
authors.lastname: Ricke
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, Harvard Stem Cell Institute, Cambridge, MA 02138, Dept. of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Ramona
authors.initials: R
authors.lastname: Pop
authors.affiliation: United States Army Institute of Environmental Medicine - Military Performance Division, Natick, MA 01760, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Carrigan
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, Harvard Stem Cell Institute, Cambridge, MA 02138, Dept. of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Gifford
authors.affiliation: United States Army Institute of Environmental Medicine - Military Performance Division, Natick, MA 01760, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Urso
authors.affiliation: United States Army Institute of Environmental Medicine - Military Performance Division, Natick, MA 01760, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kottke
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, Harvard Stem Cell Institute, Cambridge, MA 02138, Dept. of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
mesh_terms: D000818:Animals; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D035002:Lower Extremity; D008297:Male; D051379:Mice; D058977:Molecular Sequence Annotation; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D060388:Support Vector Machine; D059467:Transcriptome; D051153:Wnt Proteins / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
chemical_list: D051880:Receptors, Notch; D051153:Wnt Proteins; D003165:Complement System Proteins