Establishment of a novel disease model using disease specific iPS cells of congenital neutropenia

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591548
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Kenichiro 京都大学, 医学(系)研究科(研究院), 臨床教授 (20324634)
• Co-Investigator(Kenkyū-buntansha): 梅田 雄嗣 京都大学, 大学院医学研究科 (80397538) ; 平家 俊男 京都大学, 大学院医学研究科 (90190173)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 疾患特異的iPS細胞 / 骨髄不全 / 細胞死 / 疾患モデル

Outline of Final Research Achievements

We generated induced pluripotent stem cell lines from a patient presenting for severe congenital neutropenia with HAX1 gene deficiency and analyzed their in vitro neutrophil differentiation potential. Cytostaining and flow cytometric analyses of myeloid cells differentiated from patient-derived induced pluripotent stem cells showed arrest at the myeloid progenitor stage and apoptotic predisposition, both of which replicated abnormal granulopoiesis. Moreover, lentiviral transduction of the HAX1 cDNA into patient-derived induced pluripotent stem cells reversed disease-related abnormal granulopoiesis. This in vitro neutrophil differentiation system, which uses patient-derived induced pluripotent stem cells for disease investigation, may serve as a novel experimental model and a platform for high-throughput screening of drugs for various congenital neutrophil disorders in the future.

Free Research Field

血液学