Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells
Biallelic mutations in ATM result in the neurodegenerative syndrome Ataxia-Telangiectasia, while ATM haploinsufficiency increases the risk of cancer and other diseases. Previous studies revealed low reprogramming efficiency from A-T and carrier fibroblasts, a barrier to iPS cell-based modeling and r...
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doaj-915dc6a919d342cba723a9c48eac27412020-11-24T21:05:39ZengElsevierStem Cell Research1873-50611876-77532016-09-0117229630510.1016/j.scr.2016.08.006Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cellsNiraj Bhatt0Rajib Ghosh1Sanchita Roy2Yongxing Gao3Mary Armanios4Linzhao Cheng5Sonia Franco6Department of Radiation Oncology and Molecular Radiation Sciences, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Radiation Oncology and Molecular Radiation Sciences, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Radiation Oncology and Molecular Radiation Sciences, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADivision of Hematology, Department of Medicine, and the Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Oncology, the Sidney Kimmel Comprehensive Cancer Center and the McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADivision of Hematology, Department of Medicine, and the Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Radiation Oncology and Molecular Radiation Sciences, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USABiallelic mutations in ATM result in the neurodegenerative syndrome Ataxia-Telangiectasia, while ATM haploinsufficiency increases the risk of cancer and other diseases. Previous studies revealed low reprogramming efficiency from A-T and carrier fibroblasts, a barrier to iPS cell-based modeling and regeneration. Here, we tested the feasibility of employing circulating erythroid cells, a compartment no or minimally affected in A-T, for the generation of A-T and carrier iPS cells. Our results indicate that episomal expression of Yamanaka factors plus BCL-xL in erythroid cells results in highly efficient iPS cell production in feeder-free, xeno-free conditions. Moreover, A-T iPS cells generated with this protocol maintain long-term replicative potential, stable karyotypes, re-elongated telomeres and capability to differentiate along the neural lineage in vitro and to form teratomas in vivo. Finally, we find that haploinsufficiency for ATM does not limit reprogramming from human erythroid cells or in vivo teratoma formation in the mouse.http://www.sciencedirect.com/science/article/pii/S1873506116301052induced pluripotent stem cellsAtaxia-TelangiectasiaATMradiationtelomereteratoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Niraj Bhatt Rajib Ghosh Sanchita Roy Yongxing Gao Mary Armanios Linzhao Cheng Sonia Franco |
spellingShingle |
Niraj Bhatt Rajib Ghosh Sanchita Roy Yongxing Gao Mary Armanios Linzhao Cheng Sonia Franco Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells Stem Cell Research induced pluripotent stem cells Ataxia-Telangiectasia ATM radiation telomere teratoma |
author_facet |
Niraj Bhatt Rajib Ghosh Sanchita Roy Yongxing Gao Mary Armanios Linzhao Cheng Sonia Franco |
author_sort |
Niraj Bhatt |
title |
Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells |
title_short |
Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells |
title_full |
Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells |
title_fullStr |
Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells |
title_full_unstemmed |
Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells |
title_sort |
robust reprogramming of ataxia-telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 1876-7753 |
publishDate |
2016-09-01 |
description |
Biallelic mutations in ATM result in the neurodegenerative syndrome Ataxia-Telangiectasia, while ATM haploinsufficiency increases the risk of cancer and other diseases. Previous studies revealed low reprogramming efficiency from A-T and carrier fibroblasts, a barrier to iPS cell-based modeling and regeneration. Here, we tested the feasibility of employing circulating erythroid cells, a compartment no or minimally affected in A-T, for the generation of A-T and carrier iPS cells. Our results indicate that episomal expression of Yamanaka factors plus BCL-xL in erythroid cells results in highly efficient iPS cell production in feeder-free, xeno-free conditions. Moreover, A-T iPS cells generated with this protocol maintain long-term replicative potential, stable karyotypes, re-elongated telomeres and capability to differentiate along the neural lineage in vitro and to form teratomas in vivo. Finally, we find that haploinsufficiency for ATM does not limit reprogramming from human erythroid cells or in vivo teratoma formation in the mouse. |
topic |
induced pluripotent stem cells Ataxia-Telangiectasia ATM radiation telomere teratoma |
url |
http://www.sciencedirect.com/science/article/pii/S1873506116301052 |
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