Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures

Mark H. Chin; Mike J. Mason; Wei Xie; Stefano Volinia; Mike Singer; Cory Peterson; Gayane Ambartsumyan; Otaren Aimiuwu; Laura Richter; Jin Zhang; Ivan Khvorostov; Vanessa Ott; Michael Grunstein; Neta Lavon; Nissim Benvenisty; Carlo M. Croce; Amander T. Clark; Tim Baxter; April D. Pyle; Mike A. Teitell; Matteo Pelegrini; Kathrin Plath; William E. Lowry

doi:10.1016/j.stem.2009.06.008

Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures

Mark H. Chin, Mike J. Mason, Wei Xie, Stefano Volinia, Mike Singer, Cory Peterson, Gayane Ambartsumyan, Otaren Aimiuwu, Laura Richter, Jin Zhang, Ivan Khvorostov, Vanessa Ott, Michael Grunstein, Neta Lavon, Nissim Benvenisty, Carlo M. Croce, Amander T. Clark, Tim Baxter, April D. Pyle, Mike A. TeitellMatteo Pelegrini, Kathrin Plath^*, William E. Lowry

^*Corresponding author for this work

Department of Genetics

Research output: Contribution to journal › Article › peer-review

835 Scopus citations

Abstract

Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.

Original language	American English
Pages (from-to)	111-123
Number of pages	13
Journal	Cell Stem Cell
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/j.stem.2009.06.008
State	Published - 2 Jul 2009

Bibliographical note

Funding Information:
M.H.C. is supported by the USHHS Ruth L. Kirschstein Institutional (NRSA #T32 CA009056) and G.A. by NIH/NICHHD 5 K12 HD001281. S.V. is supported by Regione Emilia Romagna PRRIITT Biopharmanet. C.M.C. is supported by NIH-NCI. M.A.T. is supported by NIH and CIRM Grant RS1-00313. M.G. is supported by NIH GM23674. N.B. is supported by the Legacy Heritage Fund. K.P. is supported by the V and Kimmel Scholar Foundations, the NIH Director's Young Innovator Award (DP2 OD001686-01), and a CIRM Young Investigator Award (RN1-00564-1). W.E.L. holds the Maria Rowena Ross Term Chair in Cell Biology and Biochemistry and is supported by CIRM #RS1-00259-1, and the Basil O'Connor Starter Scholar Award from The March of Dimes. This work was also supported by the CIRM New Cell Line grant to Jerome Zack (UCLA), W.E.L., and K.P. (RL1-00681-1). A.T.C., A.D.P., K.P., and M.A.T. are also supported by NIH P01 GM081621-01A1.

Keywords

STEMCELL

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10.1016/j.stem.2009.06.008

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Chin, M. H., Mason, M. J., Xie, W., Volinia, S., Singer, M., Peterson, C., Ambartsumyan, G., Aimiuwu, O., Richter, L., Zhang, J., Khvorostov, I., Ott, V., Grunstein, M., Lavon, N., Benvenisty, N., Croce, C. M., Clark, A. T., Baxter, T., Pyle, A. D., ... Lowry, W. E. (2009). Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures. Cell Stem Cell, 5(1), 111-123. https://doi.org/10.1016/j.stem.2009.06.008

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abstract = "Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.",

keywords = "STEMCELL",

author = "Chin, {Mark H.} and Mason, {Mike J.} and Wei Xie and Stefano Volinia and Mike Singer and Cory Peterson and Gayane Ambartsumyan and Otaren Aimiuwu and Laura Richter and Jin Zhang and Ivan Khvorostov and Vanessa Ott and Michael Grunstein and Neta Lavon and Nissim Benvenisty and Croce, {Carlo M.} and Clark, {Amander T.} and Tim Baxter and Pyle, {April D.} and Teitell, {Mike A.} and Matteo Pelegrini and Kathrin Plath and Lowry, {William E.}",

note = "Funding Information: M.H.C. is supported by the USHHS Ruth L. Kirschstein Institutional (NRSA #T32 CA009056) and G.A. by NIH/NICHHD 5 K12 HD001281. S.V. is supported by Regione Emilia Romagna PRRIITT Biopharmanet. C.M.C. is supported by NIH-NCI. M.A.T. is supported by NIH and CIRM Grant RS1-00313. M.G. is supported by NIH GM23674. N.B. is supported by the Legacy Heritage Fund. K.P. is supported by the V and Kimmel Scholar Foundations, the NIH Director's Young Innovator Award (DP2 OD001686-01), and a CIRM Young Investigator Award (RN1-00564-1). W.E.L. holds the Maria Rowena Ross Term Chair in Cell Biology and Biochemistry and is supported by CIRM #RS1-00259-1, and the Basil O'Connor Starter Scholar Award from The March of Dimes. This work was also supported by the CIRM New Cell Line grant to Jerome Zack (UCLA), W.E.L., and K.P. (RL1-00681-1). A.T.C., A.D.P., K.P., and M.A.T. are also supported by NIH P01 GM081621-01A1. ",

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doi = "10.1016/j.stem.2009.06.008",

language = "American English",

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Chin, MH, Mason, MJ, Xie, W, Volinia, S, Singer, M, Peterson, C, Ambartsumyan, G, Aimiuwu, O, Richter, L, Zhang, J, Khvorostov, I, Ott, V, Grunstein, M, Lavon, N, Benvenisty, N, Croce, CM, Clark, AT, Baxter, T, Pyle, AD, Teitell, MA, Pelegrini, M, Plath, K & Lowry, WE 2009, 'Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures', Cell Stem Cell, vol. 5, no. 1, pp. 111-123. https://doi.org/10.1016/j.stem.2009.06.008

TY - JOUR

T1 - Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures

AU - Chin, Mark H.

AU - Mason, Mike J.

AU - Xie, Wei

AU - Volinia, Stefano

AU - Singer, Mike

AU - Peterson, Cory

AU - Ambartsumyan, Gayane

AU - Aimiuwu, Otaren

AU - Richter, Laura

AU - Zhang, Jin

AU - Khvorostov, Ivan

AU - Ott, Vanessa

AU - Grunstein, Michael

AU - Lavon, Neta

AU - Benvenisty, Nissim

AU - Croce, Carlo M.

AU - Clark, Amander T.

AU - Baxter, Tim

AU - Pyle, April D.

AU - Teitell, Mike A.

AU - Pelegrini, Matteo

AU - Plath, Kathrin

AU - Lowry, William E.

N1 - Funding Information: M.H.C. is supported by the USHHS Ruth L. Kirschstein Institutional (NRSA #T32 CA009056) and G.A. by NIH/NICHHD 5 K12 HD001281. S.V. is supported by Regione Emilia Romagna PRRIITT Biopharmanet. C.M.C. is supported by NIH-NCI. M.A.T. is supported by NIH and CIRM Grant RS1-00313. M.G. is supported by NIH GM23674. N.B. is supported by the Legacy Heritage Fund. K.P. is supported by the V and Kimmel Scholar Foundations, the NIH Director's Young Innovator Award (DP2 OD001686-01), and a CIRM Young Investigator Award (RN1-00564-1). W.E.L. holds the Maria Rowena Ross Term Chair in Cell Biology and Biochemistry and is supported by CIRM #RS1-00259-1, and the Basil O'Connor Starter Scholar Award from The March of Dimes. This work was also supported by the CIRM New Cell Line grant to Jerome Zack (UCLA), W.E.L., and K.P. (RL1-00681-1). A.T.C., A.D.P., K.P., and M.A.T. are also supported by NIH P01 GM081621-01A1.

PY - 2009/7/2

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N2 - Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.

AB - Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.

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Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures

Abstract

Bibliographical note

Keywords

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