Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased...
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Autor*in:	Itay Tirosh [verfasserIn] Andrew S Venteicher Christine Hebert Leah E Escalante Anoop P Patel Keren Yizhak Jonathan M Fisher Christopher Rodman Christopher Mount Mariella G Filbin Cyril Neftel Niyati Desai Jackson Nyman Benjamin Izar Christina C Luo Joshua M Francis Aanand A Patel Maristela L Onozato Nicolo Riggi Kenneth J Livak Dave Gennert Rahul Satija Brian V Nahed William T Curry Robert L Martuza Ravindra Mylvaganam A John Iafrate Matthew P Frosch Todd R Golub Miguel N Rivera Gad Getz Orit Rozenblatt-Rosen Daniel P Cahill Michelle Monje Bradley E Bernstein David N Louis Aviv Regev Mario L Suvà

Format:	Artikel
Sprache:	Englisch

Erschienen:	2016

Schlagwörter:	Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA

Übergeordnetes Werk:	Enthalten in: Nature - London : Macmillan Publishers Limited, part of Springer Nature, 1869, 539(2016), 7628, Seite 309-313
Übergeordnetes Werk:	volume:539 ; year:2016 ; number:7628 ; pages:309-313

Links:	Volltext Link aufrufen

DOI / URN:	10.1038/nature20123

Katalog-ID:	OLC1984930788

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520			\|a Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.
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allfields	10.1038/nature20123 doi PQ20170301 (DE-627)OLC1984930788 (DE-599)GBVOLC1984930788 (PRQ)c1465-b3cf59dff96f7a19ebe195bdf7934fa55b50e310dc5edfba3f701796bc83a6e80 (KEY)0072945020160000539762800309singlecellrnaseqsupportsadevelopmentalhierarchyinh DE-627 ger DE-627 rakwb eng 070 500 DE-101 500 AVZ BIODIV fid Itay Tirosh verfasserin aut Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management. Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA Andrew S Venteicher oth Christine Hebert oth Leah E Escalante oth Anoop P Patel oth Keren Yizhak oth Jonathan M Fisher oth Christopher Rodman oth Christopher Mount oth Mariella G Filbin oth Cyril Neftel oth Niyati Desai oth Jackson Nyman oth Benjamin Izar oth Christina C Luo oth Joshua M Francis oth Aanand A Patel oth Maristela L Onozato oth Nicolo Riggi oth Kenneth J Livak oth Dave Gennert oth Rahul Satija oth Brian V Nahed oth William T Curry oth Robert L Martuza oth Ravindra Mylvaganam oth A John Iafrate oth Matthew P Frosch oth Todd R Golub oth Miguel N Rivera oth Gad Getz oth Orit Rozenblatt-Rosen oth Daniel P Cahill oth Michelle Monje oth Bradley E Bernstein oth David N Louis oth Aviv Regev oth Mario L Suvà oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 539(2016), 7628, Seite 309-313 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:539 year:2016 number:7628 pages:309-313 http://dx.doi.org/10.1038/nature20123 Volltext http://search.proquest.com/docview/1838944275 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 539 2016 7628 309-313
spelling	10.1038/nature20123 doi PQ20170301 (DE-627)OLC1984930788 (DE-599)GBVOLC1984930788 (PRQ)c1465-b3cf59dff96f7a19ebe195bdf7934fa55b50e310dc5edfba3f701796bc83a6e80 (KEY)0072945020160000539762800309singlecellrnaseqsupportsadevelopmentalhierarchyinh DE-627 ger DE-627 rakwb eng 070 500 DE-101 500 AVZ BIODIV fid Itay Tirosh verfasserin aut Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management. Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA Andrew S Venteicher oth Christine Hebert oth Leah E Escalante oth Anoop P Patel oth Keren Yizhak oth Jonathan M Fisher oth Christopher Rodman oth Christopher Mount oth Mariella G Filbin oth Cyril Neftel oth Niyati Desai oth Jackson Nyman oth Benjamin Izar oth Christina C Luo oth Joshua M Francis oth Aanand A Patel oth Maristela L Onozato oth Nicolo Riggi oth Kenneth J Livak oth Dave Gennert oth Rahul Satija oth Brian V Nahed oth William T Curry oth Robert L Martuza oth Ravindra Mylvaganam oth A John Iafrate oth Matthew P Frosch oth Todd R Golub oth Miguel N Rivera oth Gad Getz oth Orit Rozenblatt-Rosen oth Daniel P Cahill oth Michelle Monje oth Bradley E Bernstein oth David N Louis oth Aviv Regev oth Mario L Suvà oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 539(2016), 7628, Seite 309-313 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:539 year:2016 number:7628 pages:309-313 http://dx.doi.org/10.1038/nature20123 Volltext http://search.proquest.com/docview/1838944275 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 539 2016 7628 309-313
allfields_unstemmed	10.1038/nature20123 doi PQ20170301 (DE-627)OLC1984930788 (DE-599)GBVOLC1984930788 (PRQ)c1465-b3cf59dff96f7a19ebe195bdf7934fa55b50e310dc5edfba3f701796bc83a6e80 (KEY)0072945020160000539762800309singlecellrnaseqsupportsadevelopmentalhierarchyinh DE-627 ger DE-627 rakwb eng 070 500 DE-101 500 AVZ BIODIV fid Itay Tirosh verfasserin aut Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management. Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA Andrew S Venteicher oth Christine Hebert oth Leah E Escalante oth Anoop P Patel oth Keren Yizhak oth Jonathan M Fisher oth Christopher Rodman oth Christopher Mount oth Mariella G Filbin oth Cyril Neftel oth Niyati Desai oth Jackson Nyman oth Benjamin Izar oth Christina C Luo oth Joshua M Francis oth Aanand A Patel oth Maristela L Onozato oth Nicolo Riggi oth Kenneth J Livak oth Dave Gennert oth Rahul Satija oth Brian V Nahed oth William T Curry oth Robert L Martuza oth Ravindra Mylvaganam oth A John Iafrate oth Matthew P Frosch oth Todd R Golub oth Miguel N Rivera oth Gad Getz oth Orit Rozenblatt-Rosen oth Daniel P Cahill oth Michelle Monje oth Bradley E Bernstein oth David N Louis oth Aviv Regev oth Mario L Suvà oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 539(2016), 7628, Seite 309-313 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:539 year:2016 number:7628 pages:309-313 http://dx.doi.org/10.1038/nature20123 Volltext http://search.proquest.com/docview/1838944275 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 539 2016 7628 309-313
allfieldsGer	10.1038/nature20123 doi PQ20170301 (DE-627)OLC1984930788 (DE-599)GBVOLC1984930788 (PRQ)c1465-b3cf59dff96f7a19ebe195bdf7934fa55b50e310dc5edfba3f701796bc83a6e80 (KEY)0072945020160000539762800309singlecellrnaseqsupportsadevelopmentalhierarchyinh DE-627 ger DE-627 rakwb eng 070 500 DE-101 500 AVZ BIODIV fid Itay Tirosh verfasserin aut Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management. Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA Andrew S Venteicher oth Christine Hebert oth Leah E Escalante oth Anoop P Patel oth Keren Yizhak oth Jonathan M Fisher oth Christopher Rodman oth Christopher Mount oth Mariella G Filbin oth Cyril Neftel oth Niyati Desai oth Jackson Nyman oth Benjamin Izar oth Christina C Luo oth Joshua M Francis oth Aanand A Patel oth Maristela L Onozato oth Nicolo Riggi oth Kenneth J Livak oth Dave Gennert oth Rahul Satija oth Brian V Nahed oth William T Curry oth Robert L Martuza oth Ravindra Mylvaganam oth A John Iafrate oth Matthew P Frosch oth Todd R Golub oth Miguel N Rivera oth Gad Getz oth Orit Rozenblatt-Rosen oth Daniel P Cahill oth Michelle Monje oth Bradley E Bernstein oth David N Louis oth Aviv Regev oth Mario L Suvà oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 539(2016), 7628, Seite 309-313 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:539 year:2016 number:7628 pages:309-313 http://dx.doi.org/10.1038/nature20123 Volltext http://search.proquest.com/docview/1838944275 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 539 2016 7628 309-313
allfieldsSound	10.1038/nature20123 doi PQ20170301 (DE-627)OLC1984930788 (DE-599)GBVOLC1984930788 (PRQ)c1465-b3cf59dff96f7a19ebe195bdf7934fa55b50e310dc5edfba3f701796bc83a6e80 (KEY)0072945020160000539762800309singlecellrnaseqsupportsadevelopmentalhierarchyinh DE-627 ger DE-627 rakwb eng 070 500 DE-101 500 AVZ BIODIV fid Itay Tirosh verfasserin aut Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management. Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA Andrew S Venteicher oth Christine Hebert oth Leah E Escalante oth Anoop P Patel oth Keren Yizhak oth Jonathan M Fisher oth Christopher Rodman oth Christopher Mount oth Mariella G Filbin oth Cyril Neftel oth Niyati Desai oth Jackson Nyman oth Benjamin Izar oth Christina C Luo oth Joshua M Francis oth Aanand A Patel oth Maristela L Onozato oth Nicolo Riggi oth Kenneth J Livak oth Dave Gennert oth Rahul Satija oth Brian V Nahed oth William T Curry oth Robert L Martuza oth Ravindra Mylvaganam oth A John Iafrate oth Matthew P Frosch oth Todd R Golub oth Miguel N Rivera oth Gad Getz oth Orit Rozenblatt-Rosen oth Daniel P Cahill oth Michelle Monje oth Bradley E Bernstein oth David N Louis oth Aviv Regev oth Mario L Suvà oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 539(2016), 7628, Seite 309-313 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:539 year:2016 number:7628 pages:309-313 http://dx.doi.org/10.1038/nature20123 Volltext http://search.proquest.com/docview/1838944275 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 539 2016 7628 309-313
language	English
source	Enthalten in Nature 539(2016), 7628, Seite 309-313 volume:539 year:2016 number:7628 pages:309-313
sourceStr	Enthalten in Nature 539(2016), 7628, Seite 309-313 volume:539 year:2016 number:7628 pages:309-313
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA
dewey-raw	070
isfreeaccess_bool	false
container_title	Nature
authorswithroles_txt_mv	Itay Tirosh @@aut@@ Andrew S Venteicher @@oth@@ Christine Hebert @@oth@@ Leah E Escalante @@oth@@ Anoop P Patel @@oth@@ Keren Yizhak @@oth@@ Jonathan M Fisher @@oth@@ Christopher Rodman @@oth@@ Christopher Mount @@oth@@ Mariella G Filbin @@oth@@ Cyril Neftel @@oth@@ Niyati Desai @@oth@@ Jackson Nyman @@oth@@ Benjamin Izar @@oth@@ Christina C Luo @@oth@@ Joshua M Francis @@oth@@ Aanand A Patel @@oth@@ Maristela L Onozato @@oth@@ Nicolo Riggi @@oth@@ Kenneth J Livak @@oth@@ Dave Gennert @@oth@@ Rahul Satija @@oth@@ Brian V Nahed @@oth@@ William T Curry @@oth@@ Robert L Martuza @@oth@@ Ravindra Mylvaganam @@oth@@ A John Iafrate @@oth@@ Matthew P Frosch @@oth@@ Todd R Golub @@oth@@ Miguel N Rivera @@oth@@ Gad Getz @@oth@@ Orit Rozenblatt-Rosen @@oth@@ Daniel P Cahill @@oth@@ Michelle Monje @@oth@@ Bradley E Bernstein @@oth@@ David N Louis @@oth@@ Aviv Regev @@oth@@ Mario L Suvà @@oth@@
publishDateDaySort_date	2016-01-01T00:00:00Z
hierarchy_top_id	129292834
dewey-sort	270
id	OLC1984930788
language_de	englisch
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author	Itay Tirosh
spellingShingle	Itay Tirosh ddc 070 ddc 500 fid BIODIV misc Gene expression misc Ribonucleic acid--RNA misc Stem cells misc Tumors misc Mutation misc Cancer misc RNA sequencing misc Gliomas misc Methods misc Genetic aspects misc RNA Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
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topic_title	070 500 DE-101 500 AVZ BIODIV fid Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma Gene expression Ribonucleic acid--RNA Stem cells Tumors Mutation Cancer RNA sequencing Gliomas Methods Genetic aspects RNA
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title	Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
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title_full	Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
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title_sort	single-cell rna-seq supports a developmental hierarchy in human oligodendroglioma
title_auth	Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
abstract	Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.
abstractGer	Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.
abstract_unstemmed	Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.
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title_short	Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
url	http://dx.doi.org/10.1038/nature20123 http://search.proquest.com/docview/1838944275
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up_date	2024-07-04T01:52:19.980Z
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Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. 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Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

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