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CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells

Nature Biotechnology volume 24, pages 351–357 (2006)Cite this article

Abstract

The application of human embryonic stem (hES) cells in regenerative medicine will require rigorous quality control measures to ensure the safety of hES cell–derived grafts. During propagation in vitro, hES cells can acquire cytogenetic abnormalities1,2,3 as well as submicroscopic genetic lesions, such as small amplifications or deletions4. Many of the genetic abnormalities that arise in hES cell cultures are also implicated in human cancer development. The causes of genetic instability of hES cells in culture are poorly understood, and commonly used cytogenetic methods for detection of abnormal cells are capable only of low-throughput analysis on small numbers of cells. The identification of biomarkers of genetic instability in hES cells would greatly facilitate the development of culture methods that preserve genomic integrity. Here we show that CD30, a member of the tumor necrosis factor receptor superfamily, is expressed on transformed but not normal hES cells, and that CD30 expression protects hES cells against apoptosis.

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Figure 1: Expression of CD30 transcripts and protein in human EC and ES cells.
Figure 2: Expression of CD30 in diploid or karyotypically abnormal hES cell lines.
Figure 3: Flow-cytometric analysis of CD30 expression in abnormal and diploid hES cell lines.
Figure 4: Combined analysis of CD30 expression and apoptosis in HES-2 serum replacement cultures by flow cytometry and inhibition of apoptosis by expression of CD30 variant.

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Acknowledgements

Work in the Monash Institute of Medical Research and the Australian Stem Cell Centre was supported by the National Health and Medical Research Council, The Australian Stem Cell Centre and the National Institutes of Health (NIGMS GM68417). Work in the laboratory of L.H.J.L. was supported in part by the Dutch Cancer Society/KWF.

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Author notes

  1. Benjamin E Reubinoff

    Present address: The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy and The Department of Gynecology, Hadassah University Hospital, Ein-Kerem, P.O.B. 12000, Jerusalem, 91120, Israel

  2. Daniella Herszfeld and Ernst Wolvetang: These authors contributed equally to this work.

Authors and Affiliations

  1. Monash Institute of Medical Research, Monash University, and the Australian Stem Cell Centre, Bldg. 75 STRIP, Wellington Road, Clayton, 3800, Victoria, Australia

    Daniella Herszfeld, Ernst Wolvetang, Emma Langton-Bunker, Tung-Liang Chung, Adam A Filipczyk, Souheir Houssami, Pegah Jamshidi, Karen Koh, Andrew L Laslett, Anna Michalska, Linh Nguyen, Benjamin E Reubinoff, Irene Tellis & Martin F Pera

  2. Stem Cell Center, American Type Culture Collection, 10801 University Boulevard, Manassas, 20110, Virginia, USA

    Jonathan M Auerbach & Carol J Ording

  3. Pathology/Lab. Exp. Patho-Oncology, Erasmus MC–University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Building Be, Room 430b, P.O. Box 1738, Rotterdam, 3000 DR, The Netherlands

    Leendert H J Looijenga

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Corresponding author

Correspondence to Martin F Pera.

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Competing interests

M.P. and B.R. hold shares in ES Cell International.

Supplementary information

Supplementary Fig. 1

Immunostaining of diploid ES or EC cells with antibodies to CD30. (PDF 1390 kb)

Supplementary Fig. 2

Southern analysis of CD30 gene and PCR analysis of a repeat region in its promoter in normal and GCT DNA and EC cell lines. (PDF 307 kb)

Supplementary Fig. 3

Differentiation of diploid or karyotypically abnormal hESC in vitro. (PDF 27 kb)

Supplementary Fig. 4

Differentiation of diploid or karyotypically abnormal ES or EC cells in vivo. (PDF 1412 kb)

Supplementary Fig. 5

Semiquantitative RT-PCR analysis of the expression of CD30 and CD30 variant in control and BMP-4 treated hESC. (PDF 194 kb)

Supplementary Table 1

Karyotype analysis of ES cell lines grown under different conditions. (PDF 42 kb)

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Herszfeld, D., Wolvetang, E., Langton-Bunker, E. et al. CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotechnol 24, 351–357 (2006). https://doi.org/10.1038/nbt1197

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