Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types.

Science
Authors
Keywords
Abstract

In multicellular organisms, biological function emerges when heterogeneous cell types form complex organs. Nevertheless, dissection of tissues into mixtures of cellular subpopulations is currently challenging. We introduce an automated massively parallel single-cell RNA sequencing (RNA-seq) approach for analyzing in vivo transcriptional states in thousands of single cells. Combined with unsupervised classification algorithms, this facilitates ab initio cell-type characterization of splenic tissues. Modeling single-cell transcriptional states in dendritic cells and additional hematopoietic cell types uncovers rich cell-type heterogeneity and gene-modules activity in steady state and after pathogen activation. Cellular diversity is thereby approached through inference of variable and dynamic pathway activity rather than a fixed preprogrammed cell-type hierarchy. These data demonstrate single-cell RNA-seq as an effective tool for comprehensive cellular decomposition of complex tissues.

Year of Publication
2014
Journal
Science
Volume
343
Issue
6172
Pages
776-9
Date Published
2014 Feb 14
ISSN
1095-9203
DOI
10.1126/science.1247651
PubMed ID
24531970
PubMed Central ID
PMC4412462
Links
Grant list
P50 HG006193 / HG / NHGRI NIH HHS / United States