title: Regional signals in the planarian body guide stem cell fate in the presence of genomic instability.
abstract: Cellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown. We identified a regional switch in the adult planarian body upon systemic disruption of homologous recombination with RNA-interference of Rad51 Rad51 knockdown increases DNA double-strand breaks (DSBs) throughout the body, but stem cells react differently depending on their location along the anteroposterior axis. In the presence of extensive DSBs, cells in the anterior part of the body resist death, whereas cells in the posterior region undergo apoptosis. Furthermore, we found that proliferation of cells with DNA damage is induced in the presence of brain tissue and that the retinoblastoma pathway enables overproliferation of cells with DSBs while attending to the demands of tissue growth and repair. Our results implicate both autonomous and non-autonomous mechanisms as key mediators of regional cell behavior and cellular transformation in the adult body.
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA.
authors.forename: T Harshani
authors.initials: TH
authors.lastname: Peiris
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramirez
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Barghouth
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA.
authors.forename: Udokanma
authors.initials: U
authors.lastname: Ofoha
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA.
authors.forename: Devon
authors.initials: D
authors.lastname: Davidian
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Weckerle
authors.affiliation: Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA Health Sciences Research Institute, University of California, Merced, CA 95343, USA noviedo2@ucmerced.edu.
authors.forename: Néstor J
authors.identifier: 0000-0002-0213-9781
authors.initials: NJ
authors.lastname: Oviedo
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000528:radiation effects; D016923:Cell Death / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D019070:Cell Lineage / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000528:radiation effects; D015536:Down-Regulation / Q000528:radiation effects; D005720:Gamma Rays; D042822:Genomic Instability / Q000528:radiation effects; D059765:Homologous Recombination / Q000528:radiation effects; D009928:Organ Specificity / Q000528:radiation effects; D010932:Planarians / Q000166:cytology* / Q000235:genetics* / Q000528:radiation effects; D034622:RNA Interference / Q000528:radiation effects; D051135:Rad51 Recombinase / Q000378:metabolism; D011839:Radiation, Ionizing; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D014945:Wound Healing / Q000528:radiation effects
chemical_list: D016160:Retinoblastoma Protein; D004247:DNA; D051135:Rad51 Recombinase
keywords: DNA damage; Neoblast; Planarian; Rad51; Stem cells