Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program
Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kanchan, Kanika [verfasserIn] Iyer, Kruthika [verfasserIn] Yanek, Lisa R [verfasserIn] Carcamo-Orive, Ivan [verfasserIn] Taub, Margaret A [verfasserIn] Malley, Claire [verfasserIn] Baldwin, Kristin [verfasserIn] Becker, Lewis C [verfasserIn] Broeckel, Ulrich [verfasserIn] Cheng, Linzhao [verfasserIn] Cowan, Chad [verfasserIn] D'Antonio, Matteo [verfasserIn] Frazer, Kelly A [verfasserIn] Quertermous, Thomas [verfasserIn] Mostoslavsky, Gustavo [verfasserIn] Murphy, George [verfasserIn] Rabinovitch, Marlene [verfasserIn] Rader, Daniel J [verfasserIn] Steinberg, Martin H [verfasserIn] Topol, Eric [verfasserIn] Yang, Wenli [verfasserIn] Knowles, Joshua W [verfasserIn] Jaquish, Cashell E [verfasserIn] Ruczinski, Ingo [verfasserIn] Mathias, Rasika A [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Stem cell research - Amsterdam [u.a.] : Elsevier, 2007, 46 |
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| Übergeordnetes Werk: |
volume:46 |
| DOI / URN: |
10.1016/j.scr.2020.101803 |
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| Katalog-ID: |
ELV050785583 |
|---|
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| 245 | 1 | 0 | |a Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program |
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| 520 | |a Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. | ||
| 650 | 4 | |a hiPSCs | |
| 650 | 4 | |a Structural integrity | |
| 650 | 4 | |a GWAS, VanillaICE | |
| 650 | 4 | |a Oncogenes | |
| 650 | 4 | |a Tumor suppressor genes | |
| 700 | 1 | |a Iyer, Kruthika |e verfasserin |4 aut | |
| 700 | 1 | |a Yanek, Lisa R |e verfasserin |4 aut | |
| 700 | 1 | |a Carcamo-Orive, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Taub, Margaret A |e verfasserin |4 aut | |
| 700 | 1 | |a Malley, Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Baldwin, Kristin |e verfasserin |4 aut | |
| 700 | 1 | |a Becker, Lewis C |e verfasserin |4 aut | |
| 700 | 1 | |a Broeckel, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Linzhao |e verfasserin |4 aut | |
| 700 | 1 | |a Cowan, Chad |e verfasserin |4 aut | |
| 700 | 1 | |a D'Antonio, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Frazer, Kelly A |e verfasserin |4 aut | |
| 700 | 1 | |a Quertermous, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Mostoslavsky, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, George |e verfasserin |4 aut | |
| 700 | 1 | |a Rabinovitch, Marlene |e verfasserin |4 aut | |
| 700 | 1 | |a Rader, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Steinberg, Martin H |e verfasserin |4 aut | |
| 700 | 1 | |a Topol, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Wenli |e verfasserin |4 aut | |
| 700 | 1 | |a Knowles, Joshua W |e verfasserin |4 aut | |
| 700 | 1 | |a Jaquish, Cashell E |e verfasserin |4 aut | |
| 700 | 1 | |a Ruczinski, Ingo |e verfasserin |4 aut | |
| 700 | 1 | |a Mathias, Rasika A |e verfasserin |4 aut | |
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| 912 | |a GBV_ILN_4324 | ||
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| 912 | |a GBV_ILN_4334 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4393 | ||
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10.1016/j.scr.2020.101803 doi (DE-627)ELV050785583 (ELSEVIER)S1873-5061(20)30105-7 DE-627 ger DE-627 rda eng 570 VZ Kanchan, Kanika verfasserin aut Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes Iyer, Kruthika verfasserin aut Yanek, Lisa R verfasserin aut Carcamo-Orive, Ivan verfasserin aut Taub, Margaret A verfasserin aut Malley, Claire verfasserin aut Baldwin, Kristin verfasserin aut Becker, Lewis C verfasserin aut Broeckel, Ulrich verfasserin aut Cheng, Linzhao verfasserin aut Cowan, Chad verfasserin aut D'Antonio, Matteo verfasserin aut Frazer, Kelly A verfasserin aut Quertermous, Thomas verfasserin aut Mostoslavsky, Gustavo verfasserin aut Murphy, George verfasserin aut Rabinovitch, Marlene verfasserin aut Rader, Daniel J verfasserin aut Steinberg, Martin H verfasserin aut Topol, Eric verfasserin aut Yang, Wenli verfasserin aut Knowles, Joshua W verfasserin aut Jaquish, Cashell E verfasserin aut Ruczinski, Ingo verfasserin aut Mathias, Rasika A verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 46 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:46 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 46 |
| spelling |
10.1016/j.scr.2020.101803 doi (DE-627)ELV050785583 (ELSEVIER)S1873-5061(20)30105-7 DE-627 ger DE-627 rda eng 570 VZ Kanchan, Kanika verfasserin aut Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes Iyer, Kruthika verfasserin aut Yanek, Lisa R verfasserin aut Carcamo-Orive, Ivan verfasserin aut Taub, Margaret A verfasserin aut Malley, Claire verfasserin aut Baldwin, Kristin verfasserin aut Becker, Lewis C verfasserin aut Broeckel, Ulrich verfasserin aut Cheng, Linzhao verfasserin aut Cowan, Chad verfasserin aut D'Antonio, Matteo verfasserin aut Frazer, Kelly A verfasserin aut Quertermous, Thomas verfasserin aut Mostoslavsky, Gustavo verfasserin aut Murphy, George verfasserin aut Rabinovitch, Marlene verfasserin aut Rader, Daniel J verfasserin aut Steinberg, Martin H verfasserin aut Topol, Eric verfasserin aut Yang, Wenli verfasserin aut Knowles, Joshua W verfasserin aut Jaquish, Cashell E verfasserin aut Ruczinski, Ingo verfasserin aut Mathias, Rasika A verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 46 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:46 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 46 |
| allfields_unstemmed |
10.1016/j.scr.2020.101803 doi (DE-627)ELV050785583 (ELSEVIER)S1873-5061(20)30105-7 DE-627 ger DE-627 rda eng 570 VZ Kanchan, Kanika verfasserin aut Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes Iyer, Kruthika verfasserin aut Yanek, Lisa R verfasserin aut Carcamo-Orive, Ivan verfasserin aut Taub, Margaret A verfasserin aut Malley, Claire verfasserin aut Baldwin, Kristin verfasserin aut Becker, Lewis C verfasserin aut Broeckel, Ulrich verfasserin aut Cheng, Linzhao verfasserin aut Cowan, Chad verfasserin aut D'Antonio, Matteo verfasserin aut Frazer, Kelly A verfasserin aut Quertermous, Thomas verfasserin aut Mostoslavsky, Gustavo verfasserin aut Murphy, George verfasserin aut Rabinovitch, Marlene verfasserin aut Rader, Daniel J verfasserin aut Steinberg, Martin H verfasserin aut Topol, Eric verfasserin aut Yang, Wenli verfasserin aut Knowles, Joshua W verfasserin aut Jaquish, Cashell E verfasserin aut Ruczinski, Ingo verfasserin aut Mathias, Rasika A verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 46 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:46 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 46 |
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10.1016/j.scr.2020.101803 doi (DE-627)ELV050785583 (ELSEVIER)S1873-5061(20)30105-7 DE-627 ger DE-627 rda eng 570 VZ Kanchan, Kanika verfasserin aut Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes Iyer, Kruthika verfasserin aut Yanek, Lisa R verfasserin aut Carcamo-Orive, Ivan verfasserin aut Taub, Margaret A verfasserin aut Malley, Claire verfasserin aut Baldwin, Kristin verfasserin aut Becker, Lewis C verfasserin aut Broeckel, Ulrich verfasserin aut Cheng, Linzhao verfasserin aut Cowan, Chad verfasserin aut D'Antonio, Matteo verfasserin aut Frazer, Kelly A verfasserin aut Quertermous, Thomas verfasserin aut Mostoslavsky, Gustavo verfasserin aut Murphy, George verfasserin aut Rabinovitch, Marlene verfasserin aut Rader, Daniel J verfasserin aut Steinberg, Martin H verfasserin aut Topol, Eric verfasserin aut Yang, Wenli verfasserin aut Knowles, Joshua W verfasserin aut Jaquish, Cashell E verfasserin aut Ruczinski, Ingo verfasserin aut Mathias, Rasika A verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 46 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:46 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 46 |
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10.1016/j.scr.2020.101803 doi (DE-627)ELV050785583 (ELSEVIER)S1873-5061(20)30105-7 DE-627 ger DE-627 rda eng 570 VZ Kanchan, Kanika verfasserin aut Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes Iyer, Kruthika verfasserin aut Yanek, Lisa R verfasserin aut Carcamo-Orive, Ivan verfasserin aut Taub, Margaret A verfasserin aut Malley, Claire verfasserin aut Baldwin, Kristin verfasserin aut Becker, Lewis C verfasserin aut Broeckel, Ulrich verfasserin aut Cheng, Linzhao verfasserin aut Cowan, Chad verfasserin aut D'Antonio, Matteo verfasserin aut Frazer, Kelly A verfasserin aut Quertermous, Thomas verfasserin aut Mostoslavsky, Gustavo verfasserin aut Murphy, George verfasserin aut Rabinovitch, Marlene verfasserin aut Rader, Daniel J verfasserin aut Steinberg, Martin H verfasserin aut Topol, Eric verfasserin aut Yang, Wenli verfasserin aut Knowles, Joshua W verfasserin aut Jaquish, Cashell E verfasserin aut Ruczinski, Ingo verfasserin aut Mathias, Rasika A verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 46 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:46 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 46 |
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Enthalten in Stem cell research 46 volume:46 |
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hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes |
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Kanchan, Kanika @@aut@@ Iyer, Kruthika @@aut@@ Yanek, Lisa R @@aut@@ Carcamo-Orive, Ivan @@aut@@ Taub, Margaret A @@aut@@ Malley, Claire @@aut@@ Baldwin, Kristin @@aut@@ Becker, Lewis C @@aut@@ Broeckel, Ulrich @@aut@@ Cheng, Linzhao @@aut@@ Cowan, Chad @@aut@@ D'Antonio, Matteo @@aut@@ Frazer, Kelly A @@aut@@ Quertermous, Thomas @@aut@@ Mostoslavsky, Gustavo @@aut@@ Murphy, George @@aut@@ Rabinovitch, Marlene @@aut@@ Rader, Daniel J @@aut@@ Steinberg, Martin H @@aut@@ Topol, Eric @@aut@@ Yang, Wenli @@aut@@ Knowles, Joshua W @@aut@@ Jaquish, Cashell E @@aut@@ Ruczinski, Ingo @@aut@@ Mathias, Rasika A @@aut@@ |
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2020-01-01T00:00:00Z |
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570 VZ Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program hiPSCs Structural integrity GWAS, VanillaICE Oncogenes Tumor suppressor genes |
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Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program |
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Kanchan, Kanika Iyer, Kruthika Yanek, Lisa R Carcamo-Orive, Ivan Taub, Margaret A Malley, Claire Baldwin, Kristin Becker, Lewis C Broeckel, Ulrich Cheng, Linzhao Cowan, Chad D'Antonio, Matteo Frazer, Kelly A Quertermous, Thomas Mostoslavsky, Gustavo Murphy, George Rabinovitch, Marlene Rader, Daniel J Steinberg, Martin H Topol, Eric Yang, Wenli Knowles, Joshua W Jaquish, Cashell E Ruczinski, Ingo Mathias, Rasika A |
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genomic integrity of human induced pluripotent stem cells across nine studies in the nhlbi nextgen program |
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Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program |
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Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. |
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Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. |
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Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models. |
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Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program |
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Iyer, Kruthika Yanek, Lisa R Carcamo-Orive, Ivan Taub, Margaret A Malley, Claire Baldwin, Kristin Becker, Lewis C Broeckel, Ulrich Cheng, Linzhao Cowan, Chad D'Antonio, Matteo Frazer, Kelly A Quertermous, Thomas Mostoslavsky, Gustavo Murphy, George Rabinovitch, Marlene Rader, Daniel J Steinberg, Martin H Topol, Eric Yang, Wenli Knowles, Joshua W Jaquish, Cashell E Ruczinski, Ingo Mathias, Rasika A |
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Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. 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