Simultaneous Transcriptional and Epigenomic Profiling from Specific Cell Types within Heterogeneous Tissues In Vivo

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Hyun Cheol Roh, Linus T.-Y. Tsai, Anna Lyubetskaya, Danielle Tenen, Manju Kumari, Evan D. Rosen
Epigenomic mechanisms direct distinct gene expression programs for different cell types. Various in vivo tissues have been subjected to epigenomic analysis; however, these studies have been limited by cellular heterogeneity, resulting in composite gene expression and epigenomic profiles. Here, we introduce "NuTRAP," a transgenic mouse that allows simultaneous isolation of cell-type-specific translating mRNA and chromatin from complex tissues. Using NuTRAP, we successfully characterize gene expression and epigenomic states of various adipocyte populations in vivo, revealing significant differences compared to either whole adipose tissue or in vitro adipocyte cell lines. We find that chromatin immunoprecipitation sequencing (ChIP-seq) using NuTRAP is highly efficient, scalable, and robust with even limited cell input. We further demonstrate the general utility of NuTRAP by analyzing hepatocyte-specific epigenomic states. The NuTRAP mouse is a resource that provides a powerful system for cell-type-specific gene expression and epigenomic profiling.

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Teaser

Roh et al. introduce a transgenic mouse model, named "NuTRAP," for the isolation of cell-type-specific nuclei and mRNA and characterize gene expression and epigenomic states of pure populations of adipocytes in vivo. This approach is applicable to different cell types and is highly robust even with limited cell inputs.


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