Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

Nature Medicine
Alice GiustacchiniAdam J Mead

Abstract

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustra...Continue Reading

References

Apr 5, 2001·The New England Journal of Medicine·J M Goldman, J V Melo
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Dec 17, 2008·Hematology·Catriona H Jamieson
Dec 17, 2009·PLoS Computational Biology·Daniel RamsköldRickard Sandberg
Feb 26, 2010·Nature Reviews. Immunology·Andreas TrumppAnne Wilson
Sep 10, 2010·The New England Journal of Medicine·Ramin TehranchiSten Eirik W Jacobsen
Mar 10, 2011·Nature Medicine·Hans Clevers
Jul 20, 2011·The Journal of Experimental Medicine·Cornelis J H PronkSten Eirik W Jacobsen
Sep 10, 2011·Nature Reviews. Immunology·Katherine Y King, Margaret A Goodell
Nov 8, 2011·Hematology/oncology Clinics of North America·Paolo GallipoliTessa L Holyoake
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Mar 24, 2012·Cancer Cell·Jeffrey A MageeSean J Morrison
Apr 7, 2012·Nature Protocols·Saiful IslamSten Linnarsson
Jun 12, 2012·Nature Medicine·Alex KentsisA Thomas Look
Jan 19, 2013·Leukemia·S MustjokiUNKNOWN Nordic CML Study Group (NCMLSG)
Feb 1, 2013·Development·Jing-Xia LiuWuhan Xiao
Jul 25, 2013·Frontiers in Immunology·Laura G Schuettpelz, Daniel C Link
Aug 13, 2013·Nature·Alejandra Sanjuan-PlaSten Eirik W Jacobsen
Oct 22, 2013·Nature Methods·Angela R WuStephen R Quake
Jan 5, 2014·Nature Protocols·Simone PicelliRickard Sandberg
Jun 14, 2014·Science·Anoop P PatelBradley E Bernstein
Oct 10, 2014·Nature Biotechnology·Aaron M Streets, Yanyi Huang
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Dec 18, 2014·Genome Biology·Assieh SaadatpourGuo-Cheng Yuan
Jan 15, 2015·Cancer Cell·Nicholas McGranahan, Charles Swanton
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Mar 10, 2015·Cell Stem Cell·Koen SchepersEmmanuelle Passegué
May 23, 2015·Molecular Cell·Yong Wang, Nicholas E Navin

❮ Previous
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Citations

Jun 7, 2017·Nature Medicine·Christopher A Eide, Brian J Druker
Feb 22, 2018·Biomedicines·Sarah K TasianSergio Rutella
Jan 25, 2018·Genes·Yuxuan YuanDavid Edwards
Apr 7, 2018·International Journal of Laboratory Hematology·G TangS A Wang
Feb 18, 2018·The Journal of Experimental Medicine·Ander AbarrategiDominique Bonnet
Apr 13, 2018·Proteomics·Laura MincarelliIain C Macaulay
Nov 16, 2017·Blood·Elodie GrockowiakVéronique Maguer-Satta
Jan 19, 2018·Assay and Drug Development Technologies·Eoghan O'DuibhirKamil R Kranc
Dec 23, 2017·Blood·Irene Gutierrez-Perez, Yenan T Bryceson
Nov 4, 2017·Pulmonary Circulation·Mervin C Yoder
Jan 25, 2018·Nature·Elisa Laurenti, Berthold Göttgens
Feb 8, 2019·Blood·Satyen H Gohil, Catherine J Wu
Dec 10, 2017·Hematology·Ravi Bhatia
Apr 18, 2019·JCO Clinical Cancer Informatics·Meghan C Ferrall-FairbanksPhilipp M Altrock
Aug 2, 2017·Nature Reviews. Clinical Oncology·Sam Behjati, Muzlifah Haniffa
Dec 28, 2017·Nature Reviews. Genetics·Marcin Cieślik, Arul M Chinnaiyan
Aug 3, 2019·British Journal of Haematology·Peter HoklandMarie Bill
Sep 26, 2019·Biochemical Society Transactions·Caroline Busch, Helen Wheadon
Dec 25, 2019·The Journal of Experimental Medicine·Matthew T WitkowskiIannis Aifantis
Jan 3, 2020·Current Opinion in Oncology·Charlotte K Brierley, Adam J Mead
Oct 15, 2019·British Journal of Haematology·Chia-Chen HsuChih-Cheng Chen
Jan 8, 2020·Nature Reviews. Cancer·David VetrieMhairi Copland
Mar 14, 2020·Biochemical Society Transactions·Sylvain Lefort, Véronique Maguer-Satta
Nov 16, 2017·Calcified Tissue International·Rachelle W Johnson, Larry J Suva
Jan 15, 2020·Cold Spring Harbor Perspectives in Biology·Iwo Kucinski, Berthold Gottgens
Oct 4, 2020·Nucleic Acids Research·Tianyi ZhaoJiajie Peng
Nov 30, 2018·Frontiers in Immunology·Fatima Valdes-MoraDavid Gallego-Ortega
Feb 8, 2019·Leukemia·Brooks BenardDaniel Thomas
May 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Leyuan MaMichael R Green

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