Gut Cell Atlas

About The Gut Cell Atlas

The Gut Cell Atlas initiative aims to catalogue the many cell types in the small and large intestines. The Gut Cell Atlas is part of the pathbreaking global Human Cell Atlas effort, which is transforming what we know about cells and their function in human health.

 

The Helmsley Charitable Trust is focused on finding a cure for Crohn’s disease. This is a long-term pursuit, so in parallel we are dedicated to improving patients’ lives today.

The creation of a Gut Cell Atlas, with Helmsley support, will offer tremendous potential to achieve both goals. It will enable better understanding of the disease and spur new, more personalized treatments on the path to prevention and a cure – not just for Crohn’s disease, but for improving gut health overall.

Our bodies are made of tens of trillions of cells of many different types that work together to maintain function in the face of constant change, like a fine-tuned symphony; disease occurs when these cells no longer work together in harmony.” “By building an atlas of cells in the colon of healthy individuals or individuals with Crohn’s disease, we should be able to identify key cell types involved in the disease, and understand the molecules driving their behavior, which could lead to new therapies.

Grantees

Large Scale Grants

Large Scale Grants projects focus on a variety of single-cell analyses to build a Gut Cell Atlas. Samples from both healthy individuals and those with Crohn’s disease are obtained, and data gathered for gene and protein expression and cellular localization.

Cell Type Specific Grants

Cell Type Specific Grants projects focus on particular cell types within the gut – gut-associated lymphoid tissues, enterochromaffin cells, macrophages and stem cells. Findings suggest that these cell types may play a key role in the pathology and/or symptoms of Crohn’s disease.

Technology Grants

Technology Grants projects pilot novel technologies that, if effective, will provide a new level of understanding of cellular behavior leading to intestinal inflammation.

Support Grants

Support Grants provide added tools and resources to the many activities of the Gut Cell Atlas to maximize its impact and success.

Large Scale Grants

Principal Investigator: Ramnik Xavier

“It is without question that those suffering from Crohn’s disease need better diagnostics and improved treatments. By better understanding which cells in the intestines express which genes, how these genes affect cell behavior, and which cells interact with each other, it will be possible to design new drugs and identify biomarkers to better stratify patients and improve their treatment outcomes.”

The goal of this study is to build a detailed reference atlas of the cell types, and the genes they express, of the healthy terminal ileum and ascending colon, and a corresponding reference atlas of Crohn’s disease and use them to decipher the molecular basis of intestinal function and inflammatory disease processes. This grant will also identify characteristic molecular, cellular, and histological changes in disease that can be targeted therapeutically or serve as potential biomarkers.‍

Team: Kristin Ardlie, Evan Macosko, Fei Chen, Xiaowei Zhuang, Barbara Engelhardt, Sarah Teichmann, Carl Anderson, Matthias Zilbauer

Principal Investigator: Mark Arends

“We will generate datasets that will be of use to researchers around the world for the benefit of Crohn’s disease patients.”

The goal of this study is to provide an integrated dataset of single-cell gene expression data mapped onto a high-resolution 3-dimensional framework from intestines (terminal ileum and ascending colon) of healthy individuals and Crohn’s disease patients undergoing resection due to intestinal obstruction or stricturing disease. This grant will also provide a gut-centric coordinate framework to map anatomical locations of cells providing novel insights into Crohn’s disease mechanisms, crucial to developing personalized therapeutic strategies, and new analytical tools for querying the GC database.

Team: Shahida Din, Richard Baldock, Albert Burger, Irene Papatheodorou, David Adams

Principal Investigator: Anindita (Oni) Basu

“Many complex diseases like Crohn’s disease, autism, allergies, diabetes are on the rise and as a result of our complex lifestyle. I am hopeful that the global concerted Human Cell Atlas initiative will continue to generate state-of-the-art tools and knowledge needed to understand such complex diseases and lead to treatments and prevention strategies.”

The goal of this study is to identify and characterize cell types and disease-specific gene expression patterns and regulatory features by establishing a comprehensive cellular atlas of the ileum and colon in healthy individuals and patients with ileal-colonic and ileal Crohn’s disease. This grant will also establish intestinal epithelial organoids and provide cell specific gene expression and epigenetic data to understand how similar or different these models are from the cells in the body and help explain the mechanisms of Crohn’s disease.

Team: Eugene Chang, Sebastian Pott, Matthew Stephens

Principal Investigator: Keith Wilson

“Our hope is that the Gut Cell Atlas will give us the capacity to work one cell at a time so we can develop completely new insights into the biological basis for Crohn’s disease. This should lead to out-of-the-box thinking, and thus new ways to address this debilitating disorder.”

The goal of this study is to construct an atlas of the terminal ileum and ascending colon containing single-cell gene expression and spatial information from biopsy and surgical samples from both healthy individuals and Crohn’s disease patients with varying degrees of inflammation. This grant will also provide tools to integrate the data from the multi-modality analysis of terminal ileal and colonic tissues, and related clinical data, including demographics and medications to correlate inflammation on the cellular level with patient history, symptoms and response to medications.

‍Team: Lori Coburn, Qi Liu, Ken Lau, Bennett Landman, Gregor Neuert

Principal Investigator: Jeffrey Moffitt

The goal of this study is to deliver a spatially resolved atlas of the terminal ileum to broaden our understanding of pediatric Crohn’s disease using state-of-the-art single-cell methods with a unique treatment-naïve patient cohort. If successful, this project will lead to a greater understanding of the cellular changes that occur with disease, especially in treatment naïve patients, which may lead to potential new targets for improved treatments for pediatric patients.

Team: Jose Ordovas-Montanes, Leslie Kean, Scott Snapper

Principal Investigator: Peng Qiu

“The Gut Cell Atlas, as well as the Human Cell Atlas, represent one of the forefronts of scientific research, as we try to understand complex biological systems by examining the activities and interactions of large numbers of individual cells. Studies at such a single-cell level will provide deeper understanding and generate new ideas for disease prevention and treatments.”

The goal of this study is to generate a longitudinal single-cell map of the terminal ileum and ascending colon for treatment-naïve pediatric Crohn’s disease, ultimately to observe what changes occur in inflammation and with treatment. This project will also focus on developing novel computational methods for automated cell type interpretation and single-cell analysis.

Team: Subra Kugathasan, Greg Gibson, Eliver Ghosn

 

Cell Type Specific Grants

Principal Investigator: Eugene Butcher

“The Gut Cell Atlas is part of an exciting push to catalog all the cells that make up the human body. Although only one step on the way to understanding human intestinal biology and disease, it is an important one. The Atlas will provide an essential knowledge base for understanding how ‘things go wrong’ in inflammatory bowel diseases.”

The goal of this study is to generate a comprehensive atlas of specialized immune tissues in healthy and Crohn’s disease terminal ileum and ascending colon. The investigators aim to develop methods to map cell interactions and elucidate immune cell development and trafficking in the intestinal immune response in health and Crohn’s disease.

Team: William W. Agace

Principal Investigator: Kathryn Hamilton

“There are several unresolved questions in intestinal stem cell biology, including whether there is a hierarchy of stem cells, what governs stem cell plasticity, and how stem cells survive in various injury and disease contexts. I am most excited about working with the Gut Cell Atlas consortium to address some of these unresolved questions.”

The goal of this study is to generate a comprehensive map of intestinal stem cells and their cellular signaling pathways in healthy versus Crohn’s disease biopsies from children and adults, which together with functional analyses of these cells, will support development of new strategies to heal the epithelial barrier in patients with Crohn’s disease. This grant will also define how these cell types differ between children and adults.

Team: Christopher Lengner, Judith Kelsen, Kai Tan, Meenakshi Bewtra

Principal Investigator: Guy Boeckxstaens

“Working on the Gut Cell Atlas will provide the opportunity to collect unprecedented scientific information on individual cells of the human gut both in health and in Crohn’s disease.”

The goal of this study is to characterize enterochromaffin cells and resident macrophages, two cell populations heavily involved in pain perception and immune regulation, from the terminal ileum and ascending colon of healthy individuals and Crohn’s disease patients to identify critical pathways and biomarkers involved in pain signaling and modulation of the immune response triggered by signals from the nervous system. This grant will also map specific cell types and states to their spatial locations within preserved tissue architecture to infer and characterize networks of cell-cell interactions in health and Crohn’s disease.

Team: Thierry Voet, Alejandro Sifrim, Marc Ferrante, Alexandre Denadai-Souza, Joakim Lundeberg

Technology Grants

Principal Investigator: Jellert Gaublomme

“The Gut Cell Atlas is a bold endeavor that aims to understand the cells in the gut at the single-cell level, how their organization and interactions in the gut orchestrate tissue function, and what goes awry during Crohn’s disease. The better we understand the individual components of the system, and how they work together, or cease to do so in disease, the better we’re positioned to develop effective therapies.”

The goal of this study is to develop a novel technology that enables spatially resolved high-throughput gene expression profiling of tissue sections, enabling efficient study of cell-to-cell communication mechanisms and identification of aberrations in the intestinal tissue of Crohn’s disease patients compared to healthy individuals. This grant will also provide the research community with an easily accessible tool to map spatial locations of gene transcripts within each intestinal cell and tissue.

Principal Investigator: Bobby Kasthuri

The goal of this study is to establish a sample preparation, imaging, and algorithmic pipeline to create at a micro- and nano-scale reconstructions of all the cells and their characteristics for the human enteric system and other associated tissues. This grant will provide proof of concept of the applicability of the synchrotron source X-rays and high-resolution microscopy imaging modalities to human intestinal samples and further offer a valuable anatomical map for the GC community.

Principal Investigator: Andreas Moor

“The last few years have brought unprecedented technical advances in the field of single cell genomics. These novel developments enable us to shed light on pathophysiology in disease areas with unmet medical needs.”

The goal of this study is to develop the sphere-sequencing method to systematically identify and rank cellular interactions that occur in the healthy intestine and within the Crohn’s disease microenvironment. This grant will also enable efficient study of cell-to-cell communication mechanisms by characterizing the genes expressed in each cell, the profiling of ligand – receptor pairs on neighboring cells and the corresponding spatial location of various cells.

Support Grants

Principal Investigator: Bartha Knoppers

The goal of this study is to enable rapid, international, and open-data sharing within the Human Cell Atlas (HCA) and GC communities while ensuring that data generation and use respect and protect participating individuals and patients. Harmonizing consent, privacy, security practices, access policies, and terms of use across the network will help ensure that data sharing proceeds in an effective and responsible manner and will contribute to the success of the initiative.

Team: Emily Kirby, Alex Bernier

Principal Investigator: Dermot McGovern

The goal of this study is to conduct genomic and histologic analyses on patient samples and integrate these with data from the GCA consortium to better understand which cells contribute, and how, to the diversity and progression of Crohn’s disease. If successful, this study will help better understand genetic and histological signatures as they contribute to the pathogenesis and clinical diversity observed in Crohn’s disease, and shed insight into their potential use as biomarkers in clinical practice.

Team: Arkadiusz Gertych, Talin Haritunians, Dalin Li

Principal Investigator: Lori Coburn

The goal of this project is to develop an administrative core and data repository for the GCA Consortium to enable pre-publication collaboration and sharing between GCA grantees, as well as provide general support to the activities of the GCA.

Team: Bennett Landman, Deborah Hunter, Joseph Roland

We will generate datasets that will be of use to researchers around the world for the benefit of Crohn’s disease patients.

}

Published Thu Oct 24, 2019

Scientists to Create a “Gut Cell Atlas” with Funding from the Helmsley Charitable Trust

October 25, 2019 – Today, The Leona M. and Harry B. Helmsley Charitable Trust announced $13 million in new ...
Working on the Gut Cell Atlas will provide the opportunity to collect unprecedented scientific information on individual cells of the human gut both in health and in Crohn’s disease.

The Gut Cell Atlas is an initiative supported by the Helmsley Charitable Trust Crohn’s Disease Program.

The Gut Cell Atlas is a component of the Human Cell Atlas, which seeks to create comprehensive reference maps of all cells – the fundamental units of life – as a basis for both understanding human health and diagnosing, monitoring, and treating disease.