基因在造血干细胞自我更新中的调控作用.doc

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1、基因在造血干细胞自我更新中的调控作用【摘要】造血干细胞(hematopoieticstemcell,HSC)具有高度自我更新能力和多向分化潜能，HSC的自我更新是由促进生长的正调控信号和导致凋亡的负调控信号之间的平衡来调控的。在正调控信号中，H0XB4通过激活不同的信号通路增强HSC的自我更新，同时又不影响维持正常稳态造血的调控机制。提高H0XB4的表达水平，能够极大地增强HSC的自我更新功能，但基本不影响细胞的分化、系特异性及终末细胞的形态和功能。不仅如此，H0XB4还可增强胚胎干细胞(embryonicstemcell,E

2、SC)的造血潜能，促进ESC向造血细胞分化。因此，H0XB4和H0XB4的靶基因的表迗上调可能在干细胞移植和基因治疗等方面具有广阔的应用前景。本文就H0XB4基因参与调控造血干细胞的自我更新，H0XB4对HSC的分化特异性及终末分化的“零”效应及H0XB4调控HSC自我更新的分子机制等进行综述。【关键词】H0XB4基因造血干细胞自我更新RegulatoryRoleofHOXB4inSelfrenewalofHematopoieticStemCellsReviewAbstractSelfrenewalandmu11i1ineag

3、edifferentiationofhematopoieticstemcell(HSClcharacteristics.T)arethEirfunctionaheregulationofHSCselfrenewalisgovernedbyabalancebetweenpositiveregulatorysignalspromotingegulatorysignalsris.Amongthepositiveregulatorysignalstinctpathwaysthategrowthandnegativeresultingi

4、napoptos,H0XB4activatesdisnhanceselfrenewaldivisionsofHSCwithoutoverridingtheregu1atorymechanismsthatmaintainnormalsteadystatehemopoiesis.TheupregulationofH0XB4geneexpressioncangreatlyprnewal,butdoesnotafomotetheHSCselfrefecttheHSCdifferentiation,themorphologyandfun

5、ctionof1inagespecificcellsandterminallydifferentiatedbloodcelIs.Furthermore,HOXB4canenhancethehematopoieticpotentia11(ESC),promotingtlofembryonicstemcehedifferentiationofESCintohematopoieuence,upregulationand/orcorrespondicanhaveenormoustheIforhumanHSCinthestionandg

6、enetherapyticcells.AsaconseqnofH0XB4expressiongH0XB4targetgenesrapeuticalpotentiatemcelltransplanta.Inthisreviewtheregu1atorymechanismsthatmaintainnormalsteadystatehemopoiesis.TheupregulationofH0XB4geneexpressioncangreatlyprnewal,butdoesnotafomotetheHSCselfrefectthe

7、HSCdifferentiation,themorphologyandfunctionof1inagespecificcellsandterminallydifferentiatedbloodcelIs.Furthermore,HOXB4canenhancethehematopoieticpotentia11(ESC),promotingtlofembryonicstemcehedifferentiationofESCintohematopoieuence,upregulationand/orcorrespondicanhav

8、eenormoustheIforhumanHSCinthestionandgenetherapyticcells.AsaconseqnofH0XB4expressiongH0XB4targetgenesrapeuticalpotentiatemcelltransplanta.