title: Modeling Glanzmann thrombasthenia using patient specific iPSCs and restoring platelet aggregation function by CD41 overexpression.
abstract: Glanzmann thrombasthenia (GT) is a rare monogenic hemorrhagic disorder involving aggregation defect of non-nuclear platelets. In this study we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of a GT patient with complex heterogeneous mutations of ITGA2B gene. GT-iPSCs could be successfully differentiated into platelets (GT-iPS-platelets). GT-iPS-platelets were CD41-/CD42b+/CD61- and were platelet activation marker (PAC-1) negative after adenosine diphosphate (ADP) activation. Furthermore, GT-iPS-platelets were defective in platelet aggregation tests in vitro. Moreover, exogenous expression of the wild-type ITGA2B gene in GT-iPS platelets restored CD41 expression and normal platelet aggregation. Our study suggested that patient-specific iPSCs could be a potential target of stem cell based gene therapy for platelet diseases.
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410013, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou 510150, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: National Engineering and Research Center of Human Stem Cells, Changsha 410013, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410013, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410013, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410013, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China.
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Lu
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410013, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China. Electronic address: linggf@hotmail.com.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D004252:DNA Mutational Analysis; D054641:Dual Specificity Phosphatase 2 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D039421:Integrin alpha2 / Q000235:genetics; D059785:Karyotype; D051379:Mice; D008819:Mice, Nude; D010974:Platelet Aggregation; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D013724:Teratoma / Q000378:metabolism / Q000473:pathology; D013915:Thrombasthenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C056564:ITGA2B protein, human; D039421:Integrin alpha2; D040201:Platelet Membrane Glycoprotein IIb; D014157:Transcription Factors; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2
keywords: CD41; Glanzmann thrombasthenia; Induced pluripotent stem cells; Platelet