Normal Human Pluripotent Stem Cell Lines Exhibit Pervasive Mosaic Aneuploidy
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{"title"=>"Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy", "type"=>"journal", "authors"=>[{"first_name"=>"Suzanne E.", "last_name"=>"Peterson", "scopus_author_id"=>"57024443500"}, {"first_name"=>"Jurjen W.", "last_name"=>"Westra", "scopus_author_id"=>"18438830200"}, {"first_name"=>"Stevens K.", "last_name"=>"Rehen", "scopus_author_id"=>"6602459320"}, {"first_name"=>"Holly", "last_name"=>"Young", "scopus_author_id"=>"9737287400"}, {"first_name"=>"Diane M.", "last_name"=>"Bushman", "scopus_author_id"=>"36348152400"}, {"first_name"=>"Christine M.", "last_name"=>"Paczkowski", "scopus_author_id"=>"36927201000"}, {"first_name"=>"Yun C.", "last_name"=>"Yung", "scopus_author_id"=>"8047535400"}, {"first_name"=>"Candace L.", "last_name"=>"Lynch", "scopus_author_id"=>"36935654300"}, {"first_name"=>"Ha T.", "last_name"=>"Tran", "scopus_author_id"=>"25026585900"}, {"first_name"=>"Kyle S.", "last_name"=>"Nickey", "scopus_author_id"=>"47361348600"}, {"first_name"=>"Yu Chieh", "last_name"=>"Wang", "scopus_author_id"=>"56008826600"}, {"first_name"=>"Louise C.", "last_name"=>"Laurent", "scopus_author_id"=>"23479642800"}, {"first_name"=>"Jeanne F.", "last_name"=>"Loring", "scopus_author_id"=>"7004426227"}, {"first_name"=>"Melissa K.", "last_name"=>"Carpenter", "scopus_author_id"=>"7201447653"}, {"first_name"=>"Jerold", "last_name"=>"Chun", "scopus_author_id"=>"54790495900"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"80051674461", "doi"=>"10.1371/journal.pone.0023018", "pui"=>"362343939", "pmid"=>"21857983", "scopus"=>"2-s2.0-80051674461", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"7c209592-1281-30ed-9101-53842f785ca7", "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.", "link"=>"http://www.mendeley.com/research/normal-human-pluripotent-stem-cell-lines-exhibit-pervasive-mosaic-aneuploidy-1", "reader_count"=>44, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>4, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>4, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>27, "Immunology and Microbiology"=>1, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "Ireland"=>1, "Ukraine"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/746285"], "description"=>"<p>A) Nuclei hybridized with dual point probes (red and green) for chromosome 21 and stained with DAPI (blue). Representative examples of monosomic, disomic and trisomic H7 and H9 nuclei, as well as two disomic lymphocyte nuclei are shown. B) Interphase/non-mitotic FISH analysis of H7, H9, and lymphocytes identified a statistically significant 6–7 fold increase in levels of chromosome 21 aneuploidy in hESC lines compared to lymphocytes (*p<0.001, χ<sup>2</sup>). Note that this dual point probe combination has error rates of <0.01%. C) Similar results were obtained for chromosome 4.</p>", "links"=>[], "tags"=>["hescs"], "article_id"=>416649, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FISH_analysis_of_interphase_non_mitotic_hESCs_and_lymphocytes_/416649", "title"=>"FISH analysis of interphase/non-mitotic hESCs and lymphocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-16 01:50:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/746534"], "description"=>"<p>Detailed karyotypes obtained from SKY analysis of H7, H9, and normal lymphocytes. Only numerical aneuploidies are shown, some of which included simultaneous chromosomal gains and losses. Forty chromosome spreads were analyzed for each cell type. There is no statistically significant trend in individual chromosome loss or gain. Individual chromosomes were lost and/or gained at rates of 0–4%, consistent with rates obtained from chromosome counts and FISH analysis.</p>", "links"=>[], "tags"=>["suggests", "mosaic", "aneuploidy", "stochastic"], "article_id"=>416899, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SKY_analysis_suggests_that_mosaic_aneuploidy_is_due_to_stochastic_gain_and_loss_of_chromosomes_/416899", "title"=>"SKY analysis suggests that mosaic aneuploidy is due to stochastic gain and loss of chromosomes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-16 01:54:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/746134"], "description"=>"<p>A) Example of a metaphase spread obtained from H7 cells analyzed by SKY. B) Karyotype table from the spread shown in A demonstrates that the cell had a karyotype of 42, XX, −14, −17, −20, −22.</p>", "links"=>[], "tags"=>["exhibiting", "mosaic"], "article_id"=>416495, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_SKY_analysis_exhibiting_mosaic_aneuploidy_/416495", "title"=>"Representative SKY analysis exhibiting mosaic aneuploidy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-16 01:48:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/746491"], "description"=>"<p>hPSC culture conditions are diverse. No single culture variable including medium, supplements, substrate, bFGF concentration, or passaging technique is consistent among hPSC lines showing mosaic aneuploidy. This suggests that mosaic aneuploidy is not caused by particular culture conditions. In addition, the hPSC cell lines were cultured by 6 different individuals, further suggesting that mosaic aneuploidy is not an artifact related to cell culture.</p>", "links"=>[], "tags"=>["genetics and genomics", "cell biology", "developmental biology"], "article_id"=>416848, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Culture_conditions_/416848", "title"=>"Culture conditions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-16 01:54:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/375827"], "description"=>"<div><p>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 <em>in situ</em> 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.</p> </div>", "links"=>[], "tags"=>["pluripotent", "lines", "pervasive", "mosaic", "aneuploidy"], "article_id"=>134233, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018", "stats"=>{"downloads"=>11, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Normal_Human_Pluripotent_Stem_Cell_Lines_Exhibit_Pervasive_Mosaic_Aneuploidy/134233", "title"=>"Normal Human Pluripotent Stem Cell Lines Exhibit Pervasive Mosaic Aneuploidy", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-16 01:10:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/746400"], "description"=>"<p>Mosaic aneuploidy may have both beneficial and detrimental effects - on the one hand, it may generate functional and phenotypic heterogeneity within stem cell populations leading to stable pluripotency. On the negative side, it may generate cells with a selective advantage that may be clonally expanded leading to a decrease in pluripotency and potential tumorigenicity.</p>", "links"=>[], "tags"=>["mosaic", "aneuploidy", "hpsc"], "article_id"=>416759, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_of_the_effects_of_mosaic_aneuploidy_on_hPSC_cultures_/416759", "title"=>"Model of the effects of mosaic aneuploidy on hPSC cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-16 01:52:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/746048"], "description"=>"<p>H9 (A) and H7 (B) were cultured for several passages and analyzed periodically for mosaic aneuploidy via chromosome counts. Specifically, H9 was cultured from passage 46 to 68 and analyzed at passage 46, 57 and 68. H7 was cultured from passage 51 to 64 and analyzed at passage 51, 58 and 64. Both lines show significant levels of mosaic aneuploidy at each of the passages suggesting that mosaic aneuploidy persists with time in culture. Interestingly, H9s at passage 68 were sent out for karyotyping at WiCell and they were deemed 46, XX with no abnormalities detected (black bar).</p>", "links"=>[], "tags"=>["aneuploidy", "exists"], "article_id"=>416406, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.g002", "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mosaic_aneuploidy_exists_over_time_in_culture_/416406", "title"=>"Mosaic aneuploidy exists over time in culture.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-16 01:46:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/745938"], "description"=>"<p>Metaphase chromosome spreads from H1, H7, H9, H14, Cythera25, BG01, HDF6iPS3 and human lymphocytes were stained with DAPI and chromosome numbers were counted. A representative putatively euploid metaphase spread with 46 chromosomes is shown (A) as well as an aneuploid metaphase chromosome spread with 48 chromosomes (B). C) Each metaphase spread was categorized into a bin (i.e spreads with chromosome numbers 26–30, 31–35, 36–40, 41–45, 46, 47–50 and 51–55) based on how many chromosomes it contained with chromosome numbers for each bin indicated along the x axis in the figure. Each hPSC line showed significant levels of mosaic aneuploidy ranging from 18–35%, while lymphocytes showed very low levels of aneuploidy (<3%).</p>", "links"=>[], "tags"=>["lines", "levels", "mosaic", "aneuploidy", "seen"], "article_id"=>416297, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["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"=>"https://dx.doi.org/10.1371/journal.pone.0023018.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hPSC_lines_contain_significant_levels_of_mosaic_aneuploidy_that_are_not_seen_in_human_lymphocytes_/416297", "title"=>"hPSC lines contain significant levels of mosaic aneuploidy that are not seen in human lymphocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-16 01:44:57"}

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