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The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE85157 | GEO | 2016/08/18

SECONDARY ACCESSION(S): PRJNA336350

REPOSITORIES: GEO

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The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (ChIP-Seq)

Project description:Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remain elusive. Here, we use a combination of genome-wide RNA-seq, ChIP-seq and ATAC-seq to compare the transcriptional and epigenetic identity of small intestinal ILCs, identifying thousands of distinct gene profiles and regulatory elements. Single-cell RNA-seq, cytometry, and imaging analyses reveal functional compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes, and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape, and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.

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The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (RNA-Seq)

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The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (ATAC-Seq)

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The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome

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Distinct regulatory machineries underlying divergent chromatin landscapes distinguish innate lymphoid cells from T helper cells.

Project description:Innate lymphoid cells (ILCs), as the innate counterpart of CD4+ T helper (Th) cells, play crucial roles in maintaining tissue homeostasis. While the ILC subsets and their corresponding Th subsets demonstrate significant similarities in core programming related to effector function and regulatory mechanisms, their principal distinctions, given their innate and adaptive lymphocyte nature, remain largely unknown. In this study, we have employed an integrative analysis of 294 bulk RNA-sequencing results across all ILC and Th subsets, using scRNA-seq algorithms. Consequently, we identify two genesets that predominantly differentiate ILCs from Th cells, as well as three genesets that distinguish various immune responses. Furthermore, through chromatin accessibility analysis, we find that the ILC geneset tends to rely on specific transcriptional regulation at promoter regions compared with the Th geneset. Additionally, we observe that ILCs and Th cells are under differential transcriptional regulation. For example, ILCs are under stronger regulation by multiple transcription factors, including RORα, GATA3, and NF-κB. Otherwise, Th cells are under stronger regulation by AP-1. Thus, our findings suggest that, despite the acknowledged similarities in effector functions between ILC subsets and corresponding Th subsets, the underlying regulatory machineries still exhibit substantial distinctions. These insights provide a comprehensive understanding of the unique roles played by each cell type during immune responses.

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