期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 4, 期 4, 页码 333-338出版社
ALPHAMED PRESS
DOI: 10.5966/sctm.2013-0172
关键词
Induced pluripotent stem cells; Fanconi anemia; Hematopoietic progenitors; Differentiation; Transcription factors
资金
- Ministry of Health, Labor, and Welfare
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Leading Project of MEXT
- Funding Program for World-Leading Innovative Research and Development on Science and Technology (FIRST Program) of the Japan Society for the Promotion of Science (JSPS)
- JSPS
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [20591262]
- Program for Intractable Diseases Research Utilizing Disease-Specific Induced Pluripotent Stem (iPS) Cells from the Japan Science and Technology Agency (JST)
- grant for Core Center for iPS Cell Research of Research Center Network for Realization of Regenerative Medicine from JST
- Research Grant for Intractable Diseases from the Japanese Ministry of Health, Labor, and Welfare [H-21-061]
- Grants-in-Aid for Scientific Research [25461591, 20591262, 15K06921, 26550026, 15H01738] Funding Source: KAKEN
Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF.
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