Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells

Ángel Raya; Ignasi Rodríguez-Piz; Guillermo Guenechea; Rita Vassena; Susana Navarro; María José Barrero; Antonella Consiglio; Maria Castell; Paula Río; Eduard Sleep; Federico González; Gustavo Tiscornia; Elena Garreta; Trond Aasen; Anna Veiga; Inder M. Verma; Jordi Surrallés; Juan Bueren; Juan Carlos Izpisa Belmonte

doi:10.1038/nature08129

Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells

Ángel Raya, Ignasi Rodríguez-Piz, Guillermo Guenechea, Rita Vassena, Susana Navarro, María José Barrero, Antonella Consiglio, Maria Castell, Paula Río, Eduard Sleep, Federico González, Gustavo Tiscornia, Elena Garreta, Trond Aasen, Anna Veiga, Inder M. Verma, Jordi Surrallés, Juan Bueren, Juan Carlos Izpisa Belmonte

Research output: Contribution to journal › Review article › peer-review

598 Scopus citations

Abstract

The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.

Original language	English (US)
Pages (from-to)	53-59
Number of pages	7
Journal	NATURE
Volume	460
Issue number	7251
DOIs	https://doi.org/10.1038/nature08129
State	Published - Jul 2 2009
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgements The authors are indebted to FA patients and their families for their cooperation. We are grateful to I. Badell, J. Couselo, A. Almeida and D. Schindler for collaboration in providing samples from FA patients, J.A. Casado for subtyping studies, M. Edel, J. Bilic, V. Pekarik and members of the laboratory for comments on the manuscript, J. M. Andrés-Vaquero for assistance with flow cytometry, R. Pujol for assistance with cytogenetics, M. J. Ramirez for immunofluorescence studies, B. Arán, M. Carrió and Y. Muñoz for assistance with cell culture techniques, E. Melo, L. Mulero and M. Martífor bioimaging assistance, and Y. Richaud, T. Lopez Rovira and M. L. Lozano for technical assistance. I.R.-P. and E.S. were recipients of pre-doctoral fellowships from MEC and DIUE, respectively. M.J.B. and G.T. were partially supported by the Ramón y Cajal program, and J.S. by the ICREA-Academia program. This work was partially supported by the Ministerio de Educación y Ciencia grants BFU2006-12251, SAF2005-00058, SAF2006-3440, and Genoma España (FANCOGENE), European Commission ‘Marie-Curie Reintegration Grant’ MIRG-CT-2007-046523 and European Program CONSERT LSHB-CT-2004-5242, the Fondo de Investigaciones Sanitarias (RETIC-RD06/ 0010/0016, PI061897, PI061099), Marató de TV3 (063430), the G. Harold and Leila Y. Mathers Charitable Foundation, Fundación Marcelino Botín, and Fundación Cellex.

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature08129

Cite this

Raya, Á., Rodríguez-Piz, I., Guenechea, G., Vassena, R., Navarro, S., Barrero, M. J., Consiglio, A., Castell, M., Río, P., Sleep, E., González, F., Tiscornia, G., Garreta, E., Aasen, T., Veiga, A., Verma, I. M., Surrallés, J., Bueren, J., & Belmonte, J. C. I. (2009). Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. NATURE, 460(7251), 53-59. https://doi.org/10.1038/nature08129

@article{ab59c245561447959ffb7116d1efeaf6,

title = "Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells",

abstract = "The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.",

author = "{\'A}ngel Raya and Ignasi Rodr{\'i}guez-Piz and Guillermo Guenechea and Rita Vassena and Susana Navarro and Barrero, {Mar{\'i}a Jos{\'e}} and Antonella Consiglio and Maria Castell and Paula R{\'i}o and Eduard Sleep and Federico Gonz{\'a}lez and Gustavo Tiscornia and Elena Garreta and Trond Aasen and Anna Veiga and Verma, {Inder M.} and Jordi Surrall{\'e}s and Juan Bueren and Belmonte, {Juan Carlos Izpisa}",

note = "Funding Information: Acknowledgements The authors are indebted to FA patients and their families for their cooperation. We are grateful to I. Badell, J. Couselo, A. Almeida and D. Schindler for collaboration in providing samples from FA patients, J.A. Casado for subtyping studies, M. Edel, J. Bilic, V. Pekarik and members of the laboratory for comments on the manuscript, J. M. Andr{\'e}s-Vaquero for assistance with flow cytometry, R. Pujol for assistance with cytogenetics, M. J. Ramirez for immunofluorescence studies, B. Ar{\'a}n, M. Carri{\'o} and Y. Mu{\~n}oz for assistance with cell culture techniques, E. Melo, L. Mulero and M. Mart{\'i}for bioimaging assistance, and Y. Richaud, T. Lopez Rovira and M. L. Lozano for technical assistance. I.R.-P. and E.S. were recipients of pre-doctoral fellowships from MEC and DIUE, respectively. M.J.B. and G.T. were partially supported by the Ram{\'o}n y Cajal program, and J.S. by the ICREA-Academia program. This work was partially supported by the Ministerio de Educaci{\'o}n y Ciencia grants BFU2006-12251, SAF2005-00058, SAF2006-3440, and Genoma Espa{\~n}a (FANCOGENE), European Commission {\textquoteleft}Marie-Curie Reintegration Grant{\textquoteright} MIRG-CT-2007-046523 and European Program CONSERT LSHB-CT-2004-5242, the Fondo de Investigaciones Sanitarias (RETIC-RD06/ 0010/0016, PI061897, PI061099), Marat{\'o} de TV3 (063430), the G. Harold and Leila Y. Mathers Charitable Foundation, Fundaci{\'o}n Marcelino Bot{\'i}n, and Fundaci{\'o}n Cellex.",

year = "2009",

month = jul,

day = "2",

doi = "10.1038/nature08129",

language = "English (US)",

volume = "460",

pages = "53--59",

journal = "NATURE",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7251",

}

Raya, Á, Rodríguez-Piz, I, Guenechea, G, Vassena, R, Navarro, S, Barrero, MJ, Consiglio, A, Castell, M, Río, P, Sleep, E, González, F, Tiscornia, G, Garreta, E, Aasen, T, Veiga, A, Verma, IM, Surrallés, J, Bueren, J & Belmonte, JCI 2009, 'Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells', NATURE, vol. 460, no. 7251, pp. 53-59. https://doi.org/10.1038/nature08129

TY - JOUR

T1 - Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells

AU - Raya, Ángel

AU - Rodríguez-Piz, Ignasi

AU - Guenechea, Guillermo

AU - Vassena, Rita

AU - Navarro, Susana

AU - Barrero, María José

AU - Consiglio, Antonella

AU - Castell, Maria

AU - Río, Paula

AU - Sleep, Eduard

AU - González, Federico

AU - Tiscornia, Gustavo

AU - Garreta, Elena

AU - Aasen, Trond

AU - Veiga, Anna

AU - Verma, Inder M.

AU - Surrallés, Jordi

AU - Bueren, Juan

AU - Belmonte, Juan Carlos Izpisa

N1 - Funding Information: Acknowledgements The authors are indebted to FA patients and their families for their cooperation. We are grateful to I. Badell, J. Couselo, A. Almeida and D. Schindler for collaboration in providing samples from FA patients, J.A. Casado for subtyping studies, M. Edel, J. Bilic, V. Pekarik and members of the laboratory for comments on the manuscript, J. M. Andrés-Vaquero for assistance with flow cytometry, R. Pujol for assistance with cytogenetics, M. J. Ramirez for immunofluorescence studies, B. Arán, M. Carrió and Y. Muñoz for assistance with cell culture techniques, E. Melo, L. Mulero and M. Martífor bioimaging assistance, and Y. Richaud, T. Lopez Rovira and M. L. Lozano for technical assistance. I.R.-P. and E.S. were recipients of pre-doctoral fellowships from MEC and DIUE, respectively. M.J.B. and G.T. were partially supported by the Ramón y Cajal program, and J.S. by the ICREA-Academia program. This work was partially supported by the Ministerio de Educación y Ciencia grants BFU2006-12251, SAF2005-00058, SAF2006-3440, and Genoma España (FANCOGENE), European Commission ‘Marie-Curie Reintegration Grant’ MIRG-CT-2007-046523 and European Program CONSERT LSHB-CT-2004-5242, the Fondo de Investigaciones Sanitarias (RETIC-RD06/ 0010/0016, PI061897, PI061099), Marató de TV3 (063430), the G. Harold and Leila Y. Mathers Charitable Foundation, Fundación Marcelino Botín, and Fundación Cellex.

PY - 2009/7/2

Y1 - 2009/7/2

N2 - The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.

AB - The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.

UR - http://www.scopus.com/inward/record.url?scp=67650095306&partnerID=8YFLogxK

U2 - 10.1038/nature08129

DO - 10.1038/nature08129

M3 - Review article

C2 - 19483674

AN - SCOPUS:67650095306

SN - 0028-0836

VL - 460

SP - 53

EP - 59

JO - NATURE

JF - NATURE

IS - 7251

ER -

Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this