Format

Send to

Choose Destination
Stem Cells Transl Med. 2015 Apr;4(4):333-8. doi: 10.5966/sctm.2013-0172. Epub 2015 Mar 11.

Pluripotent cell models of fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.

Author information

1
Departments of Clinical Application and.
2
Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan;
3
Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan;
4
Reprogramming Science, Center for Induced Pluripotent Stem Cell Research and Application, and Mitsubishi Space Software Co., Ltd., Amagasaki, Japan;
5
Reprogramming Science, Center for Induced Pluripotent Stem Cell Research and Application, and.
6
Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
7
Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan;
8
Departments of Clinical Application and msaito@cira.kyoto-u.ac.jp.

Abstract

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.

KEYWORDS:

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

PMID:
25762002
PMCID:
PMC4367500
DOI:
10.5966/sctm.2013-0172
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center