Your browser doesn't support javascript.
loading
Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses.
Contreras-Trujillo, Humberto; Eerdeng, Jiya; Akre, Samir; Jiang, Du; Contreras, Jorge; Gala, Basia; Vergel-Rodriguez, Mary C; Lee, Yeachan; Jorapur, Aparna; Andreasian, Areen; Harton, Lisa; Bramlett, Charles S; Nogalska, Anna; Xiao, Gang; Lee, Jae-Woong; Chan, Lai N; Müschen, Markus; Merchant, Akil A; Lu, Rong.
Afiliación
  • Contreras-Trujillo H; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Eerdeng J; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Akre S; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Jiang D; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Contreras J; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Gala B; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Vergel-Rodriguez MC; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Lee Y; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Jorapur A; Division of Hematology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Andreasian A; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Harton L; Division of Hematology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Bramlett CS; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Nogalska A; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
  • Xiao G; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale University, New Haven, CT, 06511, USA.
  • Lee JW; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale University, New Haven, CT, 06511, USA.
  • Chan LN; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale University, New Haven, CT, 06511, USA.
  • Müschen M; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale University, New Haven, CT, 06511, USA.
  • Merchant AA; Department of Immunobiology, Yale University, New Haven, CT, 06511, USA.
  • Lu R; Division of Hematology and Cellular Therapy, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. Akil.Merchant@cshs.org.
Nat Commun ; 12(1): 6522, 2021 11 11.
Article en En | MEDLINE | ID: mdl-34764253
Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de la Célula Individual / Transcriptoma Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de la Célula Individual / Transcriptoma Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido