Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy

Suzanne E. Peterson; Jurjen W. Westra; Stevens K. Rehen; Holly Young; Diane M. Bushman; Christine M. Paczkowski; Yun C. Yung; Candace L. Lynch; Ha T. Tran; Kyle S. Nickey; Yu Chieh Wang; Louise C. Laurent; Jeanne F. Loring; Melissa K. Carpenter; Jerold Chun

doi:10.1371/journal.pone.0023018

Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy

Suzanne E. Peterson, Jurjen W. Westra, Stevens K. Rehen, Holly Young, Diane M. Bushman, Christine M. Paczkowski, Yun C. Yung, Candace L. Lynch, Ha T. Tran, Kyle S. Nickey, Yu Chieh Wang, Louise C. Laurent, Jeanne F. Loring, Melissa K. Carpenter, Jerold Chun

Pharmaceutical Sciences

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

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Abstract

Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC - including induced pluripotent - lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation.

Original language	English
Article number	e23018
Journal	PLoS ONE
Volume	6
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0023018
State	Published - 2011

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Peterson, S. E., Westra, J. W., Rehen, S. K., Young, H., Bushman, D. M., Paczkowski, C. M., Yung, Y. C., Lynch, C. L., Tran, H. T., Nickey, K. S., Wang, Y. C., Laurent, L. C., Loring, J. F., Carpenter, M. K., & Chun, J. (2011). Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy. PLoS ONE, 6(8), [e23018]. https://doi.org/10.1371/journal.pone.0023018

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title = "Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy",

abstract = "Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC - including induced pluripotent - lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation.",

author = "Peterson, {Suzanne E.} and Westra, {Jurjen W.} and Rehen, {Stevens K.} and Holly Young and Bushman, {Diane M.} and Paczkowski, {Christine M.} and Yung, {Yun C.} and Lynch, {Candace L.} and Tran, {Ha T.} and Nickey, {Kyle S.} and Wang, {Yu Chieh} and Laurent, {Louise C.} and Loring, {Jeanne F.} and Carpenter, {Melissa K.} and Jerold Chun",

year = "2011",

doi = "10.1371/journal.pone.0023018",

language = "English",

volume = "6",

journal = "PLoS ONE",

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T1 - Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy

AU - Peterson, Suzanne E.

AU - Westra, Jurjen W.

AU - Rehen, Stevens K.

AU - Young, Holly

AU - Bushman, Diane M.

AU - Paczkowski, Christine M.

AU - Yung, Yun C.

AU - Lynch, Candace L.

AU - Tran, Ha T.

AU - Nickey, Kyle S.

AU - Wang, Yu Chieh

AU - Laurent, Louise C.

AU - Loring, Jeanne F.

AU - Carpenter, Melissa K.

AU - Chun, Jerold

PY - 2011

Y1 - 2011

N2 - Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC - including induced pluripotent - lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation.

AB - Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC - including induced pluripotent - lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation.

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U2 - 10.1371/journal.pone.0023018

DO - 10.1371/journal.pone.0023018

M3 - Article

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SN - 1932-6203

VL - 6

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e23018

ER -

Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy

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