Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq-Reference-Cited by-同舟云学术

Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

Published:2016-04-08 Issue:6282 Volume:352 Page:189-196
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Tirosh Itay¹,Izar Benjamin¹²³,Prakadan Sanjay M.¹⁴⁵⁶,Wadsworth Marc H.¹⁴⁵⁶,Treacy Daniel¹,Trombetta John J.¹,Rotem Asaf¹²³,Rodman Christopher¹,Lian Christine⁷,Murphy George⁷,Fallahi-Sichani Mohammad⁸,Dutton-Regester Ken¹²⁹,Lin Jia-Ren¹⁰,Cohen Ofir¹,Shah Parin²,Lu Diana¹,Genshaft Alex S.¹⁴⁵⁶,Hughes Travis K.¹⁴⁶¹¹,Ziegler Carly G. K.¹⁴⁶¹¹,Kazer Samuel W.¹⁴⁵⁶,Gaillard Aleth¹⁴⁵⁶,Kolb Kellie E.¹⁴⁵⁶,Villani Alexandra-Chloé¹,Johannessen Cory M.¹,Andreev Aleksandr Y.¹,Van Allen Eliezer M.¹²³,Bertagnolli Monica¹²¹³,Sorger Peter K.⁸¹⁰¹⁴,Sullivan Ryan J.¹⁵,Flaherty Keith T.¹⁵,Frederick Dennie T.¹⁵,Jané-Valbuena Judit¹,Yoon Charles H.¹²¹³,Rozenblatt-Rosen Orit¹,Shalek Alex K.¹⁴⁵⁶¹¹,Regev Aviv¹¹⁶¹⁷,Garraway Levi A.¹²³¹⁴

Affiliation:

1. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

3. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

4. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

5. Department of Chemistry, MIT, Cambridge, MA 02142, USA.

6. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA.

7. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

8. Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

9. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

10. HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

11. Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.

12. Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

13. Department of Surgical Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

14. Ludwig Center at Harvard, Boston, MA 02215, USA.

15. Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.

16. Department of Biology and Koch Institute, MIT, Boston, MA 02142, USA.

17. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of these differing genetic profiles within melanomas. Many cells harbored heterogeneous genetic programs that reflected two different states of genetic expression, one of which was linked to resistance development. Following drug treatment, the resistance-linked expression state was found at a much higher level. Furthermore, the environment of the melanoma cells affected their gene expression programs. Science , this issue p. 189

Funder

National Cancer Institute (NCI)

Dr. Miriam and Sheldon Adelson Medical Research Foundation

Melanoma Research Alliance

Ludwig Center at Harvard Medical School

Howard Hughes Medicine Institute

Klarman Cell Observatory

STARR Cancer Consortium

Broad Institute

Searle Scholars Program

Beckman Young Investigator Program

Dana-Farber Cancer Institute