Format

Send to

Choose Destination
Cell. 2015 Dec 3;163(6):1400-12. doi: 10.1016/j.cell.2015.11.009. Epub 2015 Nov 19.

Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity.

Author information

1
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138, USA.
2
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
3
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
4
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138, USA.
5
Department of Internal Medicine, Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
6
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
7
Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
8
Ontario Cancer Center, Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
9
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; New York Genome Center, New York, NY 10013, USA; Center for Genomics and Systems Biology, New York University, New York, NY 10012, USA.
10
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02139, USA.
11
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138, USA. Electronic address: hongkun_park@harvard.edu.
12
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Howard Hughes Medical Institute and David H. Koch Institute of Integrative Cancer Biology, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: aregev@broadinstitute.org.

Abstract

Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or differentiated in vitro under either pathogenic or non-pathogenic polarization conditions. Computational analysis relates a spectrum of cellular states in vivo to in-vitro-differentiated Th17 cells and unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four new genes: Gpr65, Plzp, Toso, and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity and can identify targets for selective suppression of pathogenic Th17 cells while potentially sparing non-pathogenic tissue-protective ones.

PMID:
26607794
PMCID:
PMC4671824
DOI:
10.1016/j.cell.2015.11.009
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center