Topic5microRNAsandCellFatemicroRNAs和细胞命运microRNAs(miRNAs)miRNAs作用机制miRNAs的生物合成过程miRNAs调节多个靶基因miRNAbiogenesisanditsregulationTechnologytostudyfunctionofmiRNAsCouplingtranscriptionalandpost‐transcriptionalmiRNAregulationinthecontrolofcellfateIncancercells,inactivationofthemiRNA-mediatedsilencingpathwayandtheavoidanceofmiRNAregulationcontributetotransformation.(A)miRNAsandTFsinFFLstendtomutuallytargetgenesfromthesamepathway.(B)Additionally,co‐regulatedmiRNAsandmiRNAfamiliesco‐targetmanygenesinthesamepathway,thusresultinginasignificanttotaloutput,havingamajoreffectoncellfate."miRNA‐targetspatiotemporalavoidance"MicroRNAsinEmbryonicStemCellsAtotalof678and472miRNAgeneshavebeendiscoveredinthehumanandmousegenomes,respectively,butonlyasubsetofthesemiRNAsisexpressedinESCs.Fewerthan100miRNAswereinitiallyidentifiedinhumanormurineEScellsbycloningandsequencingfromsmallRNAlibraries.Inindependentstudies,differentEScelllinesshowdistinctmiRNAprofiles.hsa-let-7a,hsa-miR-103,hsa-miR-130a,hsa-miR-136,hsa-miR-143,hsa-miR-151,hsamiR-16,hsa-miR-17,hsa-miR-200c,hsa-miR-21,hsa-miR-221,hsa-miR-222,hsa-miR-26a,hsa-miR-28,hsa-miR-29b,hsa-miR-301,hsa-miR-302a,hsa-miR-302b,hsa-miR-302c,hsa-miR-302d,hsa-miR-320,hsa-miR-367,hsa-miR-368,hsa-miR-371,hsa-miR-372,hsa-miR-373,hsa-miR-378,hsa-miR-423,hsamiR-425,hsa-miR-708,andhsa-miR-93miRNAsinmouseES(mES)cells1.miR-290clusteridentifiedasa2.2-kbregiononchromosome7wasdeterminedtobeES-specificbyNorthernblotting.Thesingle,spliced,cappedandpoly-adenylatedprimarytranscriptproducedatthislocusgenerateseightmaturemiRNAs(miR-290-5p,miR-290-3p,miR-291a,miR-291b,miR-292,miR-293,miR-294,miR-295),allofwhichsharesimilarsequencesanda50-proximalAAGUGCseedmotif.2.miR-302cluster(miR-302a,miR-302b,miR-302c,miR-302d,miR-367)ExpressionofthemiRNAclusterincreasedduringpreimplantationdevelopmentandremainedhighinundifferentiatedEScellsbutdecreasedafterEScelldifferentiation3.miR-17-92clusterofoncogenicmiRNAs(mir-17-3p,mir-17-5p,mir-18,mir-19a,mir-19b-1,mir-92-1)wasfoun