NIH researchers create genetic atlas detailing early stages of zebrafish development

News Release

Monday, December 18, 2023

The zebrafish is a powerful model for studying embryonic progression in vertebrates.

Researchers at the National Institutes of Health have published an atlas of zebrafish development, detailing gene expression programs activated in nearly every cell type during the first five days of development, a stage where embryos mature from one cell to different types of cells. These different cells become the tissues and organs that form the young fish that are able to swim and find food. The findings are published in Developmental Cell.

Perhaps surprisingly, the tiny zebrafish has given us important insights into human development and disease. Many of the gene expression programs that govern embryonic development are the same in fish, humans, and other animals, said Christopher McBain, Ph.D., scientific director of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which oversees the work. Because the zebrafish is very clear, fertilizes eggs externally, and is easy to study genetically, it represents a unique and effective way to model human disease.

The process of embryonic development is orchestrated by DNA instructions that direct different gene expression programs within individual cells, giving different cell types their unique functional characteristics. To create the atlas, the study team used a method called single-cell RNA sequencing to identify gene expression programs over five days, with samples taken every two to 12 hours. The resulting atlas followed nearly 490,000 cells continuously for 120 hours after fertilization, with an average of 8,621 transcripts and 1,745 genes detected per cell. The study team then sorted this data among known cell types and cell states during development.

To promote the atlas’ utility, the team focused on improving understudied cells, including intestinal cells called BEST4+ cells, which are linked to gastrointestinal diseases and cancer in humans. Little is known about how these cells develop because they are absent in other common model organisms, such as mice. Using the atlas, the team predicted the entire developmental program of BEST4+ cells, including signals that promote cell growth and transcription factors that drive the process. These findings can be evaluated in model organisms or clinical samples to better understand the role of BEST4+ cells in human disease.

Our atlas of early zebrafish development is an extremely comprehensive resource that describes the expression program of hundreds of cell types at 62 developmental stages, said senior author Jeffrey A. Farrell, Ph.D., is an Earl Stadtman Investigator and head of the NICHDs Unit on Cell Determination and Differentiation. From this atlas, we made discoveries about unstudied cells, including intestinal cells involved in human diseases, smooth muscle surrounding the intestine, and cells surrounding the blood vessel. There are many more developments waiting to be discovered, and we look forward to seeing what the research community can do with our open-source atlas.

The atlas is publicly available to the broader research community at https://daniocell.nichd.nih.gov. In addition to browsing the data online through the website, the data can also be downloaded in additional formats for reanalysis. A timelapse of early zebrafish development is available for viewing, as well as microscopy images related to the study. To learn more about the NIH Zebrafish Facility, visit the NIH Virtual Tour.

Sir A., etc. al. Single-cell analysis of shared transcriptional signatures and diversity during zebrafish development. Developmental Cell DOI: 10.1016/j.devcel.2023.11.001 (2023)

About Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD leads research and training to understand human development, improve reproductive health, improve the lives of children and adolescents, and optimize abilities for all. For more information, visit www.nichd.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and investigates the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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