Two publications in Nature report on advances from the Human Cell Atlas (HCA) consortium, creating the most comprehensive Cell Atlas of the gut to date, identifying new targets for gut diseases, and laying out a framework for expansion of the project to other parts of the anatomy. The work was carried out by researchers from the Wellcome Sanger Institute, Newcastle University, University of Cambridge, and their collaborators within the HCA.
One large-scale study mapped the cells in the human gut from early development through to adulthood. It used single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from five anatomical regions in the developing gut and a dozen distinct regions in the healthy pediatric and adult gut.
This work revealed that Crohn’s disease may be caused by activation of specific developmental pathways, and uncovered potential drug targets for treating Crohn’s and other inflammatory bowel diseases. As they write “This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells.”
The second publication describes the plan for an entire Human Developmental Cell Atlas (HDCA) of all cells that are important for healthy human development. Researchers from the HCA Developmental Biological Network and their collaborators worldwide, outline how they will create a genomic reference maps of cells, tissues and organs during different stages of healthy human development.
Rasa Elmentaite, first author on the gut study, said: “By studying multiple regions of the human gut throughout development, childhood and adulthood we’ve created a unique, detailed map of the healthy human gut. This Gut Cell Atlas reveals complex developmental events, including how the immune and nervous systems develop in the healthy gut, and identifies important differences along the intestines. The data is openly available to other researchers studying the gut, and will undoubtedly contribute to future discoveries.”
Kylie James, a senior author on that paper, who carried out the work at the Wellcome Sanger Institute, and is now at the Garvan Institute of Medical Research, Australia noted: “This Gut Cell Atlas is already shedding new light on the origins of Crohn’s and other intestinal diseases. For example, we identified three key cells that attract immune cells to form lymphoid tissue during development, and showed that this same developmental pathway may cause Crohn’s Disease.”
The gut atlas is just one example of how understanding development can shed light on disease. As the second paper describes, an effort is already underway to create an entire Human Developmental Cell Atlas (HDCA).
“The Human Developmental Cell Atlas will provide a vital resource to understand many aspects of biology and disease, in order to improve human health,” said Muzlifah Haniffa, a coordinator of the Developmental Biological Network, from Newcastle University and the Wellcome Sanger Institute, and a senior author on both papers.
Coordinated across the globe by Haniffa, Sten Linnarsson of Karolinska Institutet, and Deanne Taylor of The Children’s Hospital of Philadelphia, the HCA Developmental Biological Network will bring together many teams of researchers worldwide, sharing data and ethics resources. The cross-disciplinary community will analyze and combine data from different stages of development creating 3-dimensional organ and whole embryo maps of development across space and time.
“Creating the Human Developmental Cell Atlas is an enormously complex task, using state-of-the-art technologies. The atlas will be a hugely important resource, not only for understanding healthy development, but also for understanding many types of diseases and disorders that first manifest in children,” concluded Taylor.
