OpinionTumorFunctionalHeterogeneityUnraveledbyscRNA-seqTechnologiesLauraGonza´lez-Silva,1LauraQuevedo,1andIgnacioVarela1,*Effectivecancertreatmenthasbeenprecludedbythepresenceofvariousformsofintratumoralcomplexitythatdrivetreatmentresistanceandmetastasis.Recentsingle-cellsequencingtech-nologiesaresignificantlyfacilitatingthecharacterizationoftumorinternalarchitectureduringdiseaseprogression.Newapplicationsandadvancesoccurringatafastpacepredictanimminentbroadapplicationofthesetechnologiesinmanyresearchareas.Asoccurredwithnext-genera-tionsequencing(NGS)technologies,onceappliedtoclinicalsamplesacrosstumortypes,sin-gle-cellsequencingtechnologiescouldtriggeranexponentialincreaseinknowledgeofthemolecularpathwaysinvolvedincancerprogressionandcontributetotheimprovementofcancertreatment.MultifacetedHeterogeneityandItsImpactonCancerProgressionTumorscomprisevariouscellpopulationsinconstantevolution.SomeofthiscomplexheterogeneityderivesfromgeneticdiversificationandDarwinianselectionoftumorcellsastheyadapttovariableenvironments.Next-generationsequencing(NGS;seeGlossary)usedforthepastdecadehadenoughsensitivitytodetectmutationspresentinminorcellpopulationsand,combinedwithmulti-samplingofhumantumors(multisamplingsequencing),fosteredmanystudiesthatcharacterizedin-tratumorheterogeneityinvariouscancers[1].Thelevelofintratumorheterogeneityisconsideredamaindriveroftherapyresistanceandmetastasisandisassociatedwithpoorprognosis[2].Inaddition,humancancersfrequentlyhavetumorcellpopulationswithdifferenttranscriptionalprograms.Thisfunctionaldiversityislikelyassociatedwiththegeneticheterogeneitydescribedabovebutisalsotheresultofmanyotherfactors.First,thepresenceofahierarchicalstructure,whereagroupofquiescentstem-likecellsfostersthegrowthofatumorcomprisingcellsindifferentdifferentiationstates,wasdemon-stratedinvarioustumortypes[3].Additionally,differenttranscriptionalprogramscanbeactivatedintumorcellsasaresponsetostochasticfactorsortoavariabletumormicroenvironment.Thisfunctionaldiversitypro...
