Cellular Reprogramming toward the Erythroid Lineage英文文献资料.docVIP

HindawiPublishingCorporation InternationalJournalofCellBiology Volume2011,ArticleID501464,6pages doi:10.1155/2011/501464 ReviewArticle CellularReprogrammingtowardtheErythroidLineage LauraJ.Norton,AlisterP.W.Funnell,RichardC.M.Pearson,andMerlinCrossley SchoolofBiotechnologyandBiomolecularSciences,UniversityofNewSouthWales,Sydney,NSW2052,Australia CorrespondenceshouldbeaddressedtoMerlinCrossley,m.crossley@.au Received30March2011;Accepted8May2011 AcademicEditor:MichaelF¨oller Copyright?2011LauraJ.Nortonetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Haemoglobinopathiessuchasthalassaemiaandsicklecelldiseasepresentamajorhealthburden.Currently,themainformsof treatmentforthesediseasesarepackedredbloodcelltransfusionsandtheadministrationofdrugswhichacttononspeci?cally reactivatetheproductionoffoetalhaemoglobin.Thesetreatmentsareongoingthroughoutthelifeofthepatientandareassociated withanumberofrisks,suchaslimitationsinavailablebloodfortransfusion,infections,ironoverload,immunerejection,andside e?ectsassociatedwiththedrugtreatments.The?eldofcellularreprogramminghasadvancedsigni?cantlyinthelastfewyearsand hasrecentlyculminatedinthesuccessfulproductionoferythrocytesinculture.Thispaperwilldiscusscellularreprogramming anditspotentialrelevancetothetreatmentofhaemoglobinopathies. 1.Introduction:GlobinGeneRegulationand Haemoglobinopathies byareductionorabolitionoftheexpressionofoneormore globin genes, resulting in an imbalance of α- and β-globin chains in red blood cells and consequent anaemia [1, 4]. Sicklecellanaemiaisanotherprevalenthaemoglobinopathy and is caused by a mutation in the adult β-globin gene whichgeneratesasingleglutamicacidtovalineaminoacid substitution. This mutation leads to the polymerisation of globins in venous circulation [5, 6], which can trigger a rigid and sickled cell phenotype [7, 8] and results