Analysis of abnormal STAT1 disorders using disease-specific iPS cells.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670501
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Hiroshima University
• Principal Investigator: Kobayashi Masao 広島大学, 医歯薬保健学研究院, 教授 (00162016)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: STAT1 / iPS細胞 / 単球機能 / 破骨細胞

Outline of Final Research Achievements

This study demonstrated the establishment of the disease-specific iPS cells from patients with STAT1 abnormalities which consist of loss of function (LOF) and gain of function (GOF). Monocytes were differentiated derived from STAT1-LOF iPS cells presented the abnormal phosphorylation of STAT1 in response to IFNg. However, the change of transcriptional activity was not observed in monocytes derived from iPS cells. Osteoclasts were differentiated from bone marrow cells in patients with STAT1-LOF. The number and the activity of osteoclasts in STAT1-LOF patients were prominent, resulting in the excessive bone absorption in patients. Similar abnormality was confirmed by monocytes derived from iPS cells. These results suggest that the disease-specific iPS cells from patients with STAT1 abnormalities may be useful for the analysis of pathogenesis of STAT1-LOF and STAT1-GOF.

Free Research Field

小児科学，血液学，免疫学