A cell atlas of microbe-responsive processes in the zebrafish intestine

Reegan J. Willms; Lena O. Jones; Jennifer C. Hocking; Edan Foley

doi:10.1016/j.celrep.2022.110311

A cell atlas of microbe-responsive processes in the zebrafish intestine

Reegan J. Willms, Lena O. Jones, Jennifer C. Hocking, Edan Foley

Research output: Contribution to journal › Article › peer-review

47 Citations (SciVal)

Abstract

Gut microbial products direct growth, differentiation, and development in animal hosts. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled cell transcriptomes from the intestine, and associated tissue, of zebrafish larvae raised in the presence or absence of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome that included regulatory effects on patterning and on metabolic and immune activity. For example, we showed that the absence of microbes hindered pro-angiogenic signals in the developing vasculature, causing impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type.

Original language	English
Article number	110311
Number of pages	20
Journal	Cell Reports
Volume	38
Issue number	5
Early online date	1 Feb 2022
DOIs	https://doi.org/10.1016/j.celrep.2022.110311
Publication status	Published - 1 Feb 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Data Availability Statement

Single-cell RNA-seq raw data files have been deposited to the NCBI GEO database and are publicly available as of the date of
publication. Processed single-cell RNA-seq data have been deposited at the Broad Institute Single Cell Portal and are publicly
available as of the date of publication. Accession numbers are listed in the key resources table.
d This paper does not report original code.
d Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Acknowledgements

We acknowledge flow cytometry support from Dr. Aja Rieger and Sabina Baghirova, as well as support with single-cell library preparation from Dr. Joaquin Lopez-Orozco. Flow Cytometry Facility experiments were performed at the University of Alberta Faculty of Medicine & Dentistry Flow Cytometry Facility,
which receives financial support from the Faculty of Medicine & Dentistry
and Canada Foundation for Innovation (CFI) awards to contributing investigators. We also acknowledge imaging help from Dr. Xuejun Sun of the Department of Oncology Cell Imaging Facility and Arlene Oatway of the Department of Biological Sciences Microscopy Facility at the University of Alberta. We would also like to thank Science Animal Support Services at the University of Alberta for their excellent care of the zebrafish aquatics facility.

Funding

This work was supported by grants from the Canadian Institutes of Health Research (grant no. PJT 159604) and the Weston Family Microbiome Initiative. R.J.W. has funding support through the University of Alberta Faculty of Graduate Studies and Research, National Science and Engineering Research Council Graduate Scholarships, and Alberta Innovates Graduate Student Scholarships

Keywords

development
germ free
host-microbe interactions
intestine
microbiome
single cell
zebrafish

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2022.110311Licence: CC BY

Cite this

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A cell atlas of microbe-responsive processes in the zebrafish intestine

Abstract

Bibliographical note

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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