Cited by 2,662Pluripotent Stem Cells ResearchCRISPR and Genetic EngineeringRNA Interference and Gene Delivery

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Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA

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Warren, Luigi, Manos, Philip D., Ahfeldt, Tim, Loh, Yuin-Han, Li, Hu, Lau, Frank, Ebina, Wataru, Mandal, Pankaj K., Smith, Zachary D., Meissner, Alexander, Daley, George Q., Brack, Andrew S., Collins, James J., Cowan, Chad, Schlaeger, Thorsten M., Rossi, Derrick J.·2010·Cell Stem Cell

DOI 10.1016/j.stem.2010.08.012PMC PMC3656821

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Abstract

Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.

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Authors: Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., Daley, G. Q., Brack, A. S., Collins, J. J., Cowan, C., Schlaeger, T. M., & Rossi, D. J.
Affiliations: Boston Children's Hospital (US)
Harvard University (US)
Boston University (US)
Broad Institute (US)
Brigham and Women's Hospital (US)
Corresponding author: Rossi, Derrick J.
ORCID: Ahfeldt, Tim
Loh, Yuin-Han
Li, Hu
Lau, Frank
Ebina, Wataru
Mandal, Pankaj K.
Smith, Zachary D.
Meissner, Alexander
Daley, George Q.
Brack, Andrew S.
Collins, James J.
Schlaeger, Thorsten M.
Rossi, Derrick J.
Venue: Cell Stem Cell
Publisher: Elsevier BV
Published: 2010-11
Volume: 7
Issue: 5
Pages: 618-630
ISSN: 1875-9777 (ISSN-L)
1934-5909
DOI: 10.1016/j.stem.2010.08.012
PMC: PMC3656821
OpenAlex: W2098597036
Cited by: 2,662
References: 55
Citations by year: 2026: 74 · 2025: 67 · 2024: 89 · 2023: 81 · 2022: 109 · 2021: 153 · 2020: 148 · 2019: 130 · 2018: 178 · 2017: 167 · 2016: 201 · 2015: 208 · 2014: 235 · 2013: 264 · 2012: 288
FWCI: 106.76
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 989 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell stem cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders: Howard Hughes Medical Institute
National Heart, Lung, and Blood Institute (U01HL100001)
National Institute of Dental and Craniofacial Research (RL1DE01902, RL1DE019021)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords: synthetic mRNA, somatic cell reprogramming, pluripotency, directed differentiation, myogenesis, antiviral response, disease modeling, regenerative medicine
MeSH terms: Cell Differentiation, Cells, Cultured, Humans, RNA, Messenger, Cell Lineage, Induced Pluripotent Stem Cells, Cellular Reprogramming

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Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA

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