High-resolution transcriptome of human macrophages

PLoS One. 2012;7(9):e45466. doi: 10.1371/journal.pone.0045466. Epub 2012 Sep 21.

Abstract

Macrophages are dynamic cells integrating signals from their microenvironment to develop specific functional responses. Although, microarray-based transcriptional profiling has established transcriptional reprogramming as an important mechanism for signal integration and cell function of macrophages, current knowledge on transcriptional regulation of human macrophages is far from complete. To discover novel marker genes, an area of great need particularly in human macrophage biology but also to generate a much more thorough transcriptome of human M1- and M1-like macrophages, we performed RNA sequencing (RNA-seq) of human macrophages. Using this approach we can now provide a high-resolution transcriptome profile of human macrophages under classical (M1-like) and alternative (M2-like) polarization conditions and demonstrate a dynamic range exceeding observations obtained by previous technologies, resulting in a more comprehensive understanding of the transcriptome of human macrophages. Using this approach, we identify important gene clusters so far not appreciated by standard microarray techniques. In addition, we were able to detect differential promoter usage, alternative transcription start sites, and different coding sequences for 57 gene loci in human macrophages. Moreover, this approach led to the identification of novel M1-associated (CD120b, TLR2, SLAMF7) as well as M2-associated (CD1a, CD1b, CD93, CD226) cell surface markers. Taken together, these data support that high-resolution transcriptome profiling of human macrophages by RNA-seq leads to a better understanding of macrophage function and will form the basis for a better characterization of macrophages in human health and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Cluster Analysis
  • Exome
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • Immunophenotyping
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Macrophages / metabolism*
  • Transcriptome*

Substances

  • Lipopolysaccharide Receptors

Grant support

This work was supported by the German Research Foundation (SFB 832, SFB 704, INST 217/575-1, INST 217/576-1, INST 217/577-1), the Wilhelm-Sander-Foundation, the German Cancer Aid, the German Jose-Carreras-Foundation, the BMBF (NGFN2) (to J.L.S. and M.B.). M.R.M. has been supported by a BONFOR grant of the University of Bonn. This study was supported in part by research funding from Becton Dickinson to J.L.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.