Enteroendocrine Dynamics – New Tools Reveal Hormonal Plasticity in the Gut

Author:

Beumer Joep1ORCID,Gehart Helmuth12ORCID,Clevers Hans13ORCID

Affiliation:

1. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, CT Utrecht, The Netherlands

2. Institute for Molecular Health Sciences, ETH Zurich, Zurich, Switzerland

3. Oncode Institute, Hubrecht Institute, CT Utrecht, The Netherlands

Abstract

Abstract The recent intersection of enteroendocrine cell biology with single-cell technologies and novel in vitro model systems has generated a tremendous amount of new data. Here we highlight these recent developments and explore how these findings contribute to the understanding of endocrine lineages in the gut. In particular, the concept of hormonal plasticity, the ability of endocrine cells to produce different hormones over the course of their lifetime, challenges the classic notion of cell types. Enteroendocrine cells travel in the course of their life through different signaling environments that directly influence their hormonal repertoire. In this context, we examine how enteroendocrine cell fate is determined and modulated by signaling molecules such as bone morphogenetic proteins (BMPs) or location along the gastrointestinal tract. We analyze advantages and disadvantages of novel in vitro tools, adult stem cell or iPS-derived intestinal organoids, that have been crucial for recent findings on enteroendocrine development and plasticity. Finally, we illuminate the future perspectives of the field and discuss how understanding enteroendocrine plasticity can lead to new therapeutic approaches.

Funder

EMBO long-term fellowship

Netherlands Organization for Scientific Research

Publisher

The Endocrine Society

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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