Pluripotent Cell Models of Fanconi Anemia Identify the Early Pathological Defect in Human Hemoangiogenic Progenitors

• 渡辺, 亮

• 平家, 俊夫

• 斎藤, 潤

• Hira, Asuka

• Okada, Chihiro

• Amano, Naoki

• Watanabe, Akira

• Watanabe, Ken-ichiro

• Heike, Toshio

• Takata, Minoru

• Nakahata, Tatsutoshi

• Saito, Megumu K.

抄録

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.

収録刊行物

• Stem cells translational medicine

  Stem cells translational medicine 4 (4), 333-338, 2015-04

  Wiley-Blackwell

キーワード

• Induced pluripotent stem cells
• Fanconi anemia
• Hematopoietic progenitors
• Differentiation
• Transcription factors

詳細情報

• CRID: 1050001335841096832
• NII論文ID: 120005980869
• ISSN: 21576564
• HANDLE: 2433/218477
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles