Expression Quantitative Trait Loci Are Highly Sensitive to Cellular Differentiation State 英文参考文献.docVIP
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Expression Quantitative Trait Loci Are Highly Sensitive to Cellular Differentiation State 英文参考文献
ExpressionQuantitativeTraitLociAreHighlySensitiveto
CellularDifferentiationState
AliceGerrits1.,YangLi2.,BrunoM.Tesson2.,LeonidV.Bystrykh1,EllenWeersing1,AlbertinaAusema1,
BertDontje1,XushengWang3,4,RainerBreitling2,RitsertC.Jansen2*,GeralddeHaan1*
1Department of Cell Biology, Section Stem Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 2Groningen
BioinformaticsCentre,GroningenBiomolecularSciencesandBiotechnologyInstitute,UniversityofGroningen,Haren,TheNetherlands, 3DepartmentofAnatomyand
Neurobiology,UniversityofTennesseeHealthScienceCenter,Memphis,Tennessee,UnitedStatesofAmerica,4InstituteofBioinformatics,ZhejiangUniversity,Hangzhou,
China
Abstract
Genetical genomics is a strategy for mapping gene expression variation to expression quantitative trait loci (eQTLs). We
performedageneticalgenomicsexperimentinfourfunctionallydistinctbutdevelopmentallycloselyrelatedhematopoietic
cellpopulationsisolatedfromtheBXDpanelofrecombinantinbredmousestrains.ThisanalysisallowedustoanalyzeeQTL
robustness/sensitivityacrossdifferentcellulardifferentiationstates.Althoughweidentifiedalargenumber(365)of‘‘static’’
eQTLs that were consistently active in all four cell types, we found a much larger number (1,283) of ‘‘dynamic ’’ eQTLs
showingcell-type–dependence.Ofthese,140,45,531,and295werepreferentiallyactiveinstem,progenitor,erythroid,and
myeloidcells,respectively.AdetailedinvestigationofthosedynamiceQTLsshowedthatinmanycasestheeQTLspecificity
wasassociatedwithexpressionchangesinthetargetgene.Wefoundnoevidencefortargetgenesthatwereregulatedby
distinct eQTLs in different cell types, suggesting that large-scale changes within functional regulatory networks are
uncommon.Ourresultsdemonstratethatheritabledifferencesingeneexpressionarehighlysensitivetothedevelopmental
stageofthecellpopulationunderstudy.Therefore,futuregeneticalgenomicsstudiesshouldaimatstudyingmultiplewell-
defined and highly purified cell types in order to con
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