Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs
Jacob Hanna, Albert W. Cheng, Krishanu Saha, Jongpil Kim, Christopher J. Lengner, Frank Soldner, John P. Cassady, Julien Muffat, Bryce W. Carey, Rudolf Jaenisch
Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically convertedcellshave growth properties,an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated "naïve" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.
Published - May 18 2010
Pluripotency
10.1073/pnas.1004584107
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Mouse Embryonic Stem Cells Medicine & Life Sciences 100%
Human Embryonic Stem Cells Medicine & Life Sciences 97%
Epigenomics Medicine & Life Sciences 70%
Induced Pluripotent Stem Cells Medicine & Life Sciences 36%
Glycogen Synthase Kinase 3 Medicine & Life Sciences 21%
Germ Layers Medicine & Life Sciences 20%
Blastocyst Medicine & Life Sciences 18%
X Chromosome Medicine & Life Sciences 18%
Hanna, J., Cheng, A. W., Saha, K., Kim, J., Lengner, C. J., Soldner, F., Cassady, J. P., Muffat, J., Carey, B. W., & Jaenisch, R. (2010). Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proceedings of the National Academy of Sciences of the United States of America, 107(20), 9222-9227. https://doi.org/10.1073/pnas.1004584107
Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. / Hanna, Jacob; Cheng, Albert W.; Saha, Krishanu et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 20, 18.05.2010, p. 9222-9227.
Hanna, J, Cheng, AW, Saha, K, Kim, J, Lengner, CJ, Soldner, F, Cassady, JP, Muffat, J, Carey, BW & Jaenisch, R 2010, 'Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 20, pp. 9222-9227. https://doi.org/10.1073/pnas.1004584107
Hanna J, Cheng AW, Saha K, Kim J, Lengner CJ, Soldner F et al. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proceedings of the National Academy of Sciences of the United States of America. 2010 May 18;107(20):9222-9227. doi: 10.1073/pnas.1004584107
Hanna, Jacob ; Cheng, Albert W. ; Saha, Krishanu et al. / Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 20. pp. 9222-9227.
@article{11eaf21635d5476985252a3d1b0c6887,
title = "Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs",
abstract = "Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically convertedcellshave growth properties,an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated {"}na{\"i}ve{"} human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.",
keywords = "Pluripotency, Reprogramming",
author = "Jacob Hanna and Cheng, {Albert W.} and Krishanu Saha and Jongpil Kim and Lengner, {Christopher J.} and Frank Soldner and Cassady, {John P.} and Julien Muffat and Carey, {Bryce W.} and Rudolf Jaenisch",
doi = "10.1073/pnas.1004584107",
T1 - Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs
AU - Hanna, Jacob
AU - Cheng, Albert W.
AU - Saha, Krishanu
AU - Kim, Jongpil
AU - Lengner, Christopher J.
AU - Soldner, Frank
AU - Cassady, John P.
AU - Muffat, Julien
AU - Carey, Bryce W.
AU - Jaenisch, Rudolf
N2 - Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically convertedcellshave growth properties,an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated "naïve" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.
AB - Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically convertedcellshave growth properties,an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated "naïve" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.
KW - Pluripotency
KW - Reprogramming
U2 - 10.1073/pnas.1004584107
DO - 10.1073/pnas.1004584107