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

Stem Cells Translational Medicine
Naoya M SuzukiMegumu K Saito

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.

References

Jul 13, 2007·Sub-cellular Biochemistry·Minoru TakataMasamichi Ishiai
Apr 5, 2011·Nature Methods·Keisuke OkitaShinya Yamanaka
Jun 28, 2011·Nature Reviews. Cancer·Andrew J Deans, Stephen C West
Mar 1, 2012·Blood·Lars U W MüllerDavid A Williams
Jul 4, 2012·Genes & Development·Hyungjin Kim, Alan D D'Andrea
Jul 25, 2012·Cell Cycle·Lars U W MüllerDavid A Williams
Jan 15, 2013·Blood·Ashley N Kamimae-LanningPeter Kurre
Jan 18, 2013·Nature·Molly C Kottemann, Agata Smogorzewska
Jan 31, 2013·Development·Zengrong Zhu, Danwei Huangfu

❮ Previous
Next ❯

Citations

Oct 6, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Moonjung JungThomas Winkler
Jun 12, 2016·Trends in Molecular Medicine·Clara Soria-Valles, Carlos López-Otín
Jul 7, 2016·Stem Cells International·Takanori Eguchi, Takuo Kuboki
Aug 3, 2016·Disease Models & Mechanisms·Dido CarreroCarlos López-Otín
Oct 18, 2018·Physiological Reviews·Peter KaragiannisKenji Osafune
Oct 17, 2018·Frontiers in Immunology·Huensuk Kim, Christoph Schaniel
Jun 7, 2019·Disease Models & Mechanisms·Maria Georgomanoli, Eirini P Papapetrou
Aug 28, 2019·Cold Spring Harbor Perspectives in Medicine·Eirini P Papapetrou
Nov 25, 2020·Cell Stem Cell·Sonya Ruiz-TorresSusanne I Wells
Apr 7, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Chinnadurai ManiKomaraiah Palle

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Related Papers

The Journal of Clinical Endocrinology and Metabolism
Neelam GiriConstantine A Stratakis
Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
K Sue O'Shea, Melvin G McInnis
© 2021 Meta ULC. All rights reserved