Series 09 September 2021

Cell & developmental biology in the digestive system

The gastrointestinal system comprises a plethora of different cell types that develop, interact, specialize and function in a complex, tightly regulated process and, in many cases, show remarkable plasticity. In this article series, Nature Reviews Gastroenterology & Hepatology explores different cell biology and developmental pathways involved in gastrointestinal health and disease, the role of stem and progenitor cells in tissue development and regeneration and recent advances in bioengineering, which might shape clinical approaches in the near future.

Content

Cell senescence in liver diseases: pathological mechanism and theranostic opportunity

Ageing and senescence are major risk factors for liver disease development. This Review provides a comprehensive overview of hepatic senescence, its role in liver disease progression and hepatocellular carcinoma, and discusses potential therapeutic strategies.
- David Sanfeliu-Redondo
- Albert Gibert-Ramos
- Jordi Gracia-Sancho
Review Article14 Mar 2024 Nature Reviews Gastroenterology & Hepatology
A Roadmap for the Human Gut Cell Atlas

Single-cell profiling studies of the human gastrointestinal tract are increasing, offering an excellent opportunity to generate the first Human Gut Cell Atlas. This Roadmap presents a structured direction towards this goal and provides a detailed overview of the major challenges.
- Matthias Zilbauer
- Kylie R. James
- Human Cell Atlas Gut Biological Network Consortium
Roadmap31 May 2023 Nature Reviews Gastroenterology & Hepatology
Building gut from scratch — progress and update of intestinal tissue engineering

Intestinal tissue engineering offers a potential therapeutic option for short bowel syndrome. This Review examines the progress in intestinal tissue engineering, discusses the components required for engineered intestinal grafts, preclinical progress and efforts towards clinical translation, including challenges to overcome.
- Lucinda Tullie
- Brendan C. Jones
- Vivian S. W. Li
Review Article3 Mar 2022 Nature Reviews Gastroenterology & Hepatology
Hippo signalling in the liver: role in development, regeneration and disease

In this Review, Russell and Camargo summarize the role of the Hippo signalling pathway in liver development, homeostasis, regeneration and disease, and discuss development of potential therapeutics for liver diseases such as fibrosis and cancer.
- Jacquelyn O. Russell
- Fernando D. Camargo
Review Article21 Jan 2022 Nature Reviews Gastroenterology & Hepatology
Cancer stem cells in hepatocellular carcinoma — from origin to clinical implications

The complexity of hepatocellular carcinoma (HCC) hinders effective treatment. Here, Lee and colleagues summarize cancer stem cell (CSC) origin and plasticity, CSC–immune system interactions and the effects of the microenvironmental niche on cancer stemness in HCC. Potential CSC-based therapies for HCC are also presented.
- Terence Kin-Wah Lee
- Xin-Yuan Guan
- Stephanie Ma
Review Article9 Sep 2021 Nature Reviews Gastroenterology & Hepatology
Role of liver sinusoidal endothelial cells in liver diseases

Liver sinusoidal endothelial cells (LSECs) form the wall of the hepatic sinusoids and have essential roles in hepatic homeostasis. This Review describes the phenotypic dysregulations of LSECs in the context of liver disease and hepatocellular carcinoma, and provides an update of the role of LSECs as therapeutic targets.
- Jordi Gracia-Sancho
- Esther Caparrós
- Rubén Francés
Review Article15 Feb 2021 Nature Reviews Gastroenterology & Hepatology
Liver regeneration: biological and pathological mechanisms and implications

The liver has a broad range of regenerative capacities. In this Review, Michalopoulos and Bhushan describe the regenerative mechanisms employed by hepatic cells after liver injury as well as the experimental models used to investigate these mechanisms and discuss the clinical implications.
- George K. Michalopoulos
- Bharat Bhushan
Review Article6 Aug 2020 Nature Reviews Gastroenterology & Hepatology
Spatial heterogeneity in the mammalian liver

Key hepatic functions are expressed non-uniformly across liver lobules, a phenomenon termed zonation. Here, Ben-Moshe and Itzkovitz discuss the principles of liver zonation, the intrinsic and extrinsic factors that dictate zonation patterns and new genomic approaches for studying zonation of parenchymal and non-parenchymal cells
- Shani Ben-Moshe
- Shalev Itzkovitz
Review Article1 Apr 2019 Nature Reviews Gastroenterology & Hepatology
Cholangiocyte pathobiology

Cholangiocytes, which line the intrahepatic and extrahepatic bile ducts, are specialized cells that regulate bile production and homeostasis. Here, the authors discuss the role of cholangiocytes in development and liver regeneration, inflammation and fibrosis and their interactions with the immune system.
- Jesus M. Banales
- Robert C. Huebert
- Gregory J. Gores
Review Article8 Mar 2019 Nature Reviews Gastroenterology & Hepatology
Updates on hepatic homeostasis and the many tiers of hepatobiliary repair

Deciphering the complex circuitry of liver homeostasis and repair is required to improve regenerative therapies for hepatic diseases. Studies in 2018 have identified subsets of hepatic cells that have unique reparative abilities and clarified the role of biomechanical forces and hepatobiliary reprogramming as sustainable modes of tissue repair.
- Satdarshan P. Monga
Year in Review10 Dec 2018 Nature Reviews Gastroenterology & Hepatology
Tales from the crypt: new insights into intestinal stem cells

The intestinal epithelium undergoes constant replenishment, fuelled by continuously dividing stem cells residing in crypts. In this Review, Gehart and Clevers discuss the signals, cell types and mechanisms that control intestinal stem cell homeostasis and explore how imbalance in key signalling pathways can cause disease.
- Helmuth Gehart
- Hans Clevers
Review Article14 Nov 2018 Nature Reviews Gastroenterology & Hepatology
Acid and the basis for cellular plasticity and reprogramming in gastric repair and cancer

The stomach responds to injury via two main patterns, the superficial response and the glandular response. In this Review, Sáenz and Mills discuss cellular plasticity and reprogramming in the stomach in the context of disease (such as gastric cancer) and during repair and homeostasis.
- José B. Sáenz
- Jason C. Mills
Review Article21 Feb 2018 Nature Reviews Gastroenterology & Hepatology
Regenerative medicine and cell-based approaches to restore pancreatic function

Endocrine (such as diabetes) and exocrine (such as pancreatitis) disorders of the pancreas have a substantial burden worldwide. This Review explores the potential of regenerative medicine and cell-based approaches to restore both endocrine and exocrine pancreatic function, describing insights into cell replacement, implantation and reprogramming.
- Cara Ellis
- Adam Ramzy
- Timothy J. Kieffer
Review Article16 Aug 2017 Nature Reviews Gastroenterology & Hepatology
Mechanisms of hepatic stellate cell activation

Activation of hepatic stellate cells (HSCs) in liver injury is the primary driver of hepatic fibrosis. In this Review, Tsuchida and Friedman detail the varied intracellular and extracellular signalling pathways leading to HSC activation, as well as the role of HSCs in liver fibrosis resolution and as therapeutic targets.
- Takuma Tsuchida
- Scott L. Friedman
Review Article10 May 2017 Nature Reviews Gastroenterology & Hepatology
Human mini-guts: new insights into intestinal physiology and host–pathogen interactions

The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research. This Review highlights the uses of enteroids, colonoids and organoids in functional transport physiology studies and host–pathogen studies.
- Julie G. In
- Jennifer Foulke-Abel
- Mark Donowitz
Review Article28 Sep 2016 Nature Reviews Gastroenterology & Hepatology
Bioengineering the gut: future prospects of regenerative medicine

Resection of the diseased gastrointestinal tract can lead to surgical complications and low quality of life. In this Review, Bitar summarizes advances in gastrointestinal tissue engineering and regenerative medicine that aim to overcome these complications and restore tissue function.
- Khalil N. Bitar
- Elie Zakhem
Review Article10 Aug 2016 Nature Reviews Gastroenterology & Hepatology
Liver regeneration — mechanisms and models to clinical application

Liver regeneration is important in both the context of homeostasis and in recovery from disease or injury. In this Review, Forbes and Newsome describe the mechanisms underlying liver regeneration and the experimental models used to study this process, as well as discussing how liver regeneration is clinically relevant.
- Stuart J. Forbes
- Philip N. Newsome
Review Article29 Jun 2016 Nature Reviews Gastroenterology & Hepatology
The Hippo pathway in intestinal regeneration and disease

The Hippo signalling cascade is crucial for the maintenance of tissue homeostasis and regeneration after damage. This Review describes the core components of the Hippo pathway and their role in intestinal homeostasis, regeneration and disease, and the integration of Hippo signalling with other key signalling pathways. The function of the Hippo pathway in liver physiology and disease is briefly discussed.
- Audrey W. Hong
- Zhipeng Meng
- Kun-Liang Guan
Review Article5 May 2016 Nature Reviews Gastroenterology & Hepatology
Plasticity of the brush border — the yin and yang of intestinal homeostasis

The intestinal brush border consists of an array of densely packed microvilli that regulate absorption of nutrients. In this Review, the authors provide an overview of the many components that form the highly organized brush border domain and discuss pathological causes and consequences of a loss of brush border integrity.
- Delphine Delacour
- Julie Salomon
- Daniel Louvard
Review Article3 Feb 2016 Nature Reviews Gastroenterology & Hepatology

Cell & developmental biology in the digestive system

Content

Cell senescence in liver diseases: pathological mechanism and theranostic opportunity

A Roadmap for the Human Gut Cell Atlas

Building gut from scratch — progress and update of intestinal tissue engineering

Hippo signalling in the liver: role in development, regeneration and disease

Cancer stem cells in hepatocellular carcinoma — from origin to clinical implications

Role of liver sinusoidal endothelial cells in liver diseases

Liver regeneration: biological and pathological mechanisms and implications

Spatial heterogeneity in the mammalian liver

Cholangiocyte pathobiology

Updates on hepatic homeostasis and the many tiers of hepatobiliary repair

Tales from the crypt: new insights into intestinal stem cells

Acid and the basis for cellular plasticity and reprogramming in gastric repair and cancer

Regenerative medicine and cell-based approaches to restore pancreatic function

Mechanisms of hepatic stellate cell activation

Human mini-guts: new insights into intestinal physiology and host–pathogen interactions

Bioengineering the gut: future prospects of regenerative medicine

Liver regeneration — mechanisms and models to clinical application

The Hippo pathway in intestinal regeneration and disease

Plasticity of the brush border — the yin and yang of intestinal homeostasis

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