Hematopoietic abnormalities and susceptibility to infection involving SAMD9 gene mutations

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08206
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto University
• Principal Investigator: KAWASAKI Yuri 京都大学, iPS細胞研究所, 特定研究員 (70507079)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: SAMD9 / MIRAGE症候群 / iPS細胞

Outline of Final Research Achievements

Cell proliferation was compared between wild-type and mutant of the SAMD9 gene. As a result, there was no significant difference between wild-type and mutant iPS cells. However, in iPS-ML cells, proliferation was more strongly suppressed in the order wild-type > heterozygous > mutant homozygous. This suggests that the hematopoietic abnormality of MIRAGE syndrome is due to the suppression of proliferation during hematopoietic differentiation stage.
The iPS-MP cells were stimulated with inducers of cytokines, and cytokine levels were measured. As a result, disease-specific iPS-MP cells showed higher levels of cytokines than healthy human-derived iPS-MP cells. The abnormal production of the elevated cytokines is suggested to be caused by the SAMD9 gene mutation.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

iPS細胞を応用し発展させた細胞に単球系の細胞株であるiPS-ML細胞と、マクロファージ様の細胞であるiPS-MP細胞がある。これらの細胞は遺伝子変異が原因で発症する患者から作製することができ、細胞レベルでの病態再現に役立つ。今回、これらの細胞をMIRAGE症候群の研究に適用し新たな知見を得た。MIRAGE症候群の患者は症状の重い小児であるため、患者から研究のために十分な量の血液を採取することは非常に困難である。また、治療の影響を受けている患者の血液細胞を用いた研究とは違い、治療の影響や患者の体内環境の影響を除外できるiPS-ML細胞およびiPS-MP細胞の研究への応用は非常に有用であった。