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Epigenetics. 2018;13(3):264-274. doi: 10.1080/15592294.2018.1441650. Epub 2018 May 10.

Global, integrated analysis of methylomes and transcriptomes from laser capture microdissected bronchial and alveolar cells in human lung.

Author information

1
a Department of Genetics , Albert Einstein College of Medicine , 1301 Morris Park Ave, Bronx , New York 10461 , USA.
2
b Department of Medicine , Albert Einstein College of Medicine , 1301 Morris Park Ave, Bronx , New York 10461 , USA.
3
c Department of Computational Intelligence and Systems Science , Tokyo Institute of Technology , 4259 Nagatsuta-cho, Midori-ku, Yokohama , Kanagawa 226-8502 , Japan.
4
d Department of Epidemiology & Population Health , Albert Einstein College of Medicine , 1301 Morris Park Ave, Bronx , New York 10461 , USA.
5
e Department of Ophthalmology & Visual Sciences , Albert Einstein College of Medicine , 1301 Morris Park Ave, Bronx , New York 10461 , USA.

Abstract

Gene regulatory analysis of highly diverse human tissues in vivo is essentially constrained by the challenge of performing genome-wide, integrated epigenetic and transcriptomic analysis in small selected groups of specific cell types. Here we performed genome-wide bisulfite sequencing and RNA-seq from the same small groups of bronchial and alveolar cells isolated by laser capture microdissection from flash-frozen lung tissue of 12 donors and their peripheral blood T cells. Methylation and transcriptome patterns differed between alveolar and bronchial cells, while each of these epithelia showed more differences from mesodermally-derived T cells. Differentially methylated regions (DMRs) between alveolar and bronchial cells tended to locate at regulatory regions affecting promoters of 4,350 genes. A large number of pathways enriched for these DMRs including GTPase signal transduction, cell death, and skeletal muscle. Similar patterns of transcriptome differences were observed: 4,108 differentially expressed genes (DEGs) enriched in GTPase signal transduction, inflammation, cilium assembly, and others. Prioritizing using DMR-DEG regulatory network, we highlighted genes, e.g., ETS1, PPARG, and RXRG, at prominent alveolar vs. bronchial cell discriminant nodes. Our results show that multi-omic analysis of small, highly specific cells is feasible and yields unique physiologic loci distinguishing human lung cell types in situ.

KEYWORDS:

RNA sequencing; alveolar cell; bronchial cell; laser capture microdissection; whole-genome bisulfite sequencing

PMID:
29465290
PMCID:
PMC5997142
DOI:
10.1080/15592294.2018.1441650
[Indexed for MEDLINE]
Free PMC Article

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