TORC1 is required to balance cell proliferation and cell death in planarians

摘要

Multicellularorganismsareequippedwithcellularmechanismsthatenablethemtoreplacedifferentiatedcellslosttonormalphysiologicalturnover,injury,andforsomesuchasplanarians,evenamputation.Thisprocessoftissuehomeostasisisgenerallymediatedbyadultstemcells(ASCs),tissue-specificstemcellsresponsibleformaintaininganatomicalformandfunction.Todoso,ASCsmustmodulatethebalancebetweencellproliferation,i.e.inresponsetonutrients,andthatofcelldeath,i.e.inresponsetostarvationorinjury.Buthowthesetwoantagonisticprocessesarecoordinatedremainsunclear.Here,weexploretheroleofthecorecomponentsoftheTORpathwayduringplanariantissuehomeostasisandregenerationandidentifiedanessentialfunctionforTORC1inthesetwoprocesses.RNAi-mediatedsilencingofemTOR/eminintactanimalsresultedinasignificantincreaseincelldeath,whereasstemcellproliferationandstemcellmaintenancewereunaffected.Amputatedanimalsfailedtoincreasestemcellproliferationafterwoundinganddisplayeddefectsintissueremodeling.Together,ourfindingssuggesttwodistinctrolesforTORC1inplanarians.TORC1isrequiredtomodulatethebalancebetweencellproliferationandcelldeathduringnormalcellturnoverandinresponsetonutrients.Inaddition,itisrequiredtoinitiateappropriatestemcellproliferationduringregenerationandforpropertissueremodelingtooccurtomaintainscaleandproportion./p/div