title: Simultaneous Transcriptional and Epigenomic Profiling from Specific Cell Types within Heterogeneous Tissues In Vivo.
abstract: 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.
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Roh
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Linus T-Y
authors.initials: LT
authors.lastname: Tsai
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lyubetskaya
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Tenen
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Manju
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA. Electronic address: erosen@bidmc.harvard.edu.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Rosen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D047369:Chromatin Immunoprecipitation; D057890:Epigenomics; D005821:Genetic Techniques; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D006657:Histones; D012333:RNA, Messenger
keywords: ChIP-seq; NuTRAP; RNA-seq; adipocyte; epigenomics