Leveraging single-cell genomics for cell therapy in Huntington's disease

Abstract

brain regions,particularlyaffectingthestriatalneuronsknownasMediumSpinyNeurons(MSNs). Unfortunately,neuronsdonotregenerate,thus,makingitimpossibleforthebodytoreplacetheir function. Despiteextensiveresearch,thereiscurrentlynocureforHD,andthegoaloftreatmentis to alleviatesymptoms. Stem celltherapyrepresentsapromisingdirection,allowingindefinite in vitro cells expansionand differentiationintothedesiredtargetneurons.Themainlimitationofneuralcellstransplantisthat once theirprojectionsaregrown,theycannotbedetractedfromthecultureplatewithoutbreaking and causingcelldeath. In thisproject,wefocusonidentifyingtheoptimaltargetprogenitorsubpopulation.Thecellsshould be matureenoughtoexclusivelydifferentiateintoMSNsbutyetnotoverlymature,preventingthe development oftheprojectionsthatleadtocelldeathuponbreaking.Leveragingcomputational genomics, weanalyzehumansingle-cellRNAsequencingdatatocharacterizetheMSNdifferen- tiation process.Integrating in vivo and in vitro data, wegroupcellsindifferentclustersdepending on theirgeneticexpressionandcomputetheirvelocitiestoanalysetheirfate.Ourfindingsreveala potential groupofcellsthatseemtofulfillallthecriteria.Additionally,theprojecthasenabledthe characterization ofthedifferentlineagesofcellswithinthedifferentiationprocessofstriatalneurons.