Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish

Author:

Rubin Sara A.123ORCID,Baron Chloé S.13ORCID,Pessoa Rodrigues Cecilia13ORCID,Duran Madeleine4ORCID,Corbin Alexandra F.1ORCID,Yang Song P.1ORCID,Trapnell Cole4ORCID,Zon Leonard I.1235ORCID

Affiliation:

1. Stem Cell Program and Division of Hematology/Oncology, Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston, MA 1

2. Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 2

3. Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA 3

4. Department of Genome Sciences, University of Washington, Seattle, WA 4

5. Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 5

Abstract

The zebrafish has proven to be a valuable model organism for studying hematopoiesis, but relatively little is known about zebrafish immune cell development and functional diversity. Elucidating key aspects of zebrafish lymphocyte development and exploring the breadth of effector functions would provide valuable insight into the evolution of adaptive immunity. We performed single-cell RNA sequencing on ∼70,000 cells from the zebrafish marrow and thymus to establish a gene expression map of zebrafish immune cell development. We uncovered rich cellular diversity in the juvenile and adult zebrafish thymus, elucidated B- and T-cell developmental trajectories, and transcriptionally characterized subsets of hematopoietic stem and progenitor cells and early thymic progenitors. Our analysis permitted the identification of two dendritic-like cell populations and provided evidence in support of the existence of a pre-B cell state. Our results provide critical insights into the landscape of zebrafish immunology and offer a foundation for cellular and genetic studies.

Funder

National Heart, Lung, and Blood Institute

Human Frontier Science Program

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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