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Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion.
Satpathy, Ansuman T; Granja, Jeffrey M; Yost, Kathryn E; Qi, Yanyan; Meschi, Francesca; McDermott, Geoffrey P; Olsen, Brett N; Mumbach, Maxwell R; Pierce, Sarah E; Corces, M Ryan; Shah, Preyas; Bell, Jason C; Jhutty, Darisha; Nemec, Corey M; Wang, Jean; Wang, Li; Yin, Yifeng; Giresi, Paul G; Chang, Anne Lynn S; Zheng, Grace X Y; Greenleaf, William J; Chang, Howard Y.
Afiliação
  • Satpathy AT; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Granja JM; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Yost KE; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Qi Y; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Meschi F; Biophysics Program, Stanford University School of Medicine, Stanford, CA, USA.
  • McDermott GP; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Olsen BN; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Mumbach MR; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA.
  • Pierce SE; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Corces MR; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA.
  • Shah P; 10x Genomics, Inc., Pleasanton, CA, USA.
  • Bell JC; 10x Genomics, Inc., Pleasanton, CA, USA.
  • Jhutty D; 10x Genomics, Inc., Pleasanton, CA, USA.
  • Nemec CM; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Wang J; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Wang L; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Yin Y; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Giresi PG; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Chang ALS; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA.
  • Zheng GXY; 10x Genomics, Inc., Pleasanton, CA, USA.
  • Greenleaf WJ; 10x Genomics, Inc., Pleasanton, CA, USA.
  • Chang HY; 10x Genomics, Inc., Pleasanton, CA, USA.
Nat Biotechnol ; 37(8): 925-936, 2019 08.
Article em En | MEDLINE | ID: mdl-31375813
Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here, we assess the performance of a massively parallel droplet-based method for mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq). We apply scATAC-seq to obtain chromatin profiles of more than 200,000 single cells in human blood and basal cell carcinoma. In blood, application of scATAC-seq enables marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity and reconstruction of trajectories of cellular differentiation. In basal cell carcinoma, application of scATAC-seq reveals regulatory networks in malignant, stromal and immune cells in the tumor microenvironment. Analysis of scATAC-seq profiles from serial tumor biopsies before and after programmed cell death protein 1 blockade identifies chromatin regulators of therapy-responsive T cell subsets and reveals a shared regulatory program that governs intratumoral CD8+ T cell exhaustion and CD4+ T follicular helper cell development. We anticipate that scATAC-seq will enable the unbiased discovery of gene regulatory factors across diverse biological systems.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células da Medula Óssea / Cromatina / Linfócitos T / Análise de Célula Única Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Biotechnol Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células da Medula Óssea / Cromatina / Linfócitos T / Análise de Célula Única Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Biotechnol Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos