Transit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition

Laura E Sanman; Ina W Chen; Jake M Bieber; Veronica Steri; Coralie Trentesaux; Byron Hann; Ophir D Klein; Lani F Wu; Steven J Altschuler

doi:10.1016/j.devcel.2020.12.020

Transit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition

Dev Cell. 2021 Feb 8;56(3):356-365.e9. doi: 10.1016/j.devcel.2020.12.020. Epub 2021 Jan 22.

Authors

Laura E Sanman¹, Ina W Chen¹, Jake M Bieber², Veronica Steri³, Coralie Trentesaux⁴, Byron Hann³, Ophir D Klein⁵, Lani F Wu⁶, Steven J Altschuler⁷

Affiliations

¹ Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
² Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, San Francisco, CA 94158, USA.
³ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Preclinical Therapeutics Core, University of California, San Francisco, San Francisco, CA 94158, USA.
⁴ Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
⁵ Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
⁶ Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: lani.wu@ucsf.edu.
⁷ Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: steven.altschuler@ucsf.edu.

Abstract

Renewing tissues have the remarkable ability to continually produce both proliferative progenitor and specialized differentiated cell types. How are complex milieus of microenvironmental signals interpreted to coordinate tissue-cell-type composition? Here, we investigate the responses of intestinal epithelium to individual and paired perturbations across eight epithelial signaling pathways. Using a high-throughput approach that combines enteroid monolayers and quantitative imaging, we identified conditions that enrich for specific cell types as well as interactions between pathways. Importantly, we found that modulation of transit-amplifying cell proliferation changes the ratio of differentiated secretory to absorptive cell types. These observations highlight an underappreciated role for transit-amplifying cells in the tuning of differentiated cell-type composition.

Keywords: cell-type composition; high-throughput platform; intestinal epithelium; lineage model; organoid; systems biology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cell Proliferation
Epithelial Cells / cytology*
Epithelial Cells / metabolism
ErbB Receptors / metabolism
Humans
Interleukin-4 / metabolism
Intestinal Absorption
Intestines / cytology*
Male
Mice
Mice, Inbred C57BL
Models, Biological
Organoids / cytology
Protein Interaction Mapping
Signal Transduction

Substances

Interleukin-4
ErbB Receptors

Abstract

Publication types

MeSH terms

Substances

Grants and funding