The cellular states and fates of shed intestinal cells

Keren Bahar Halpern; Yael Korem Kohanim; Adi Biram; Yotam Harnik; Adi Egozi; Oran Yakubovsky; Ziv Shulman; Shalev Itzkovitz

doi:10.1038/s42255-023-00905-9

The cellular states and fates of shed intestinal cells

Keren Bahar Halpern^*, Yael Korem Kohanim, Adi Biram, Yotam Harnik, Adi Egozi, Oran Yakubovsky, Ziv Shulman, Shalev Itzkovitz^*

^*Corresponding author for this work

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

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Abstract

The intestinal epithelium is replaced every few days¹. Enterocytes are shed into the gut lumen predominantly from the tips of villi^2,3 and have been believed to rapidly die upon their dissociation from the tissue^4,5. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.

Original language	English
Pages (from-to)	1858-1869
Number of pages	12
Journal	Nature metabolism
Volume	5
Issue number	11
Early online date	19 Oct 2023
DOIs	https://doi.org/10.1038/s42255-023-00905-9
Publication status	Published - Nov 2023

Funding

We thank H. Shapiro and E. Elinav from the department of Systems Immunology, Weizmann Institute of Science, for help with experimental procedures of mice perturbations. We thank Y. Levin and A. Savidor from the INCPM proteomics unit, Weizmann Institute of Science, for help with the proteomics experiment. Y.K.K is supported by the JSMF Postdoctoral Fellowship in Understanding Dynamic and Multi-scale Systems (Award # https://doi.org/10.37717/2020-1428 ). S.I. is supported by the Moross Integrated Cancer Center, the Yad Abraham Research Center for Cancer Diagnostics and Therapy, the Helen and Martin Kimmel Institute for Stem Cell Research, the Minerva Stiftung grant, the Israel Science Foundation grants no. 908/21 and no. 3663/21, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant no. 768956, a Weizmann-Sheba joint research grant and a research grant from the Ministry of Innovation, Science and Technology, Israel. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

All Science Journal Classification (ASJC) codes

Internal Medicine
Endocrinology, Diabetes and Metabolism
Physiology (medical)
Cell Biology

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10.1038/s42255-023-00905-9

is_Nat-Meta_The-cellular-states_AM_2023Accepted author manuscript, 141 KBLicence: Unspecified

Cite this

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title = "The cellular states and fates of shed intestinal cells",

abstract = "The intestinal epithelium is replaced every few days 1. Enterocytes are shed into the gut lumen predominantly from the tips of villi 2,3 and have been believed to rapidly die upon their dissociation from the tissue 4,5. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.",

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AU - Bahar Halpern, Keren

AU - Korem Kohanim, Yael

AU - Biram, Adi

AU - Harnik, Yotam

AU - Egozi, Adi

AU - Yakubovsky, Oran

AU - Shulman, Ziv

AU - Itzkovitz, Shalev

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The cellular states and fates of shed intestinal cells

Abstract

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