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

Sara A Rubin, Chlo�� S Baron, Cecilia Pessoa Rodrigues, Madeleine Duran, Alexandra F Corbin, Song P Yang, Cole Trapnell, Leonard I Zon
Author Information
  1. Sara A Rubin: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  2. Chlo�� S Baron: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  3. Cecilia Pessoa Rodrigues: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  4. Madeleine Duran: Department of Genome Sciences, University of Washington, Seattle, WA. ORCID
  5. Alexandra F Corbin: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  6. Song P Yang: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  7. Cole Trapnell: Department of Genome Sciences, University of Washington, Seattle, WA. ORCID
  8. Leonard I Zon: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID

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.

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Grants

  1. F30 HL152628/NHLBI NIH HHS
  2. P01 HL131477/NHLBI NIH HHS
  3. R01 HL144780/NHLBI NIH HHS
  4. T32 HL007574/NHLBI NIH HHS

MeSH Term

Animals
Hematopoiesis
Hematopoietic Stem Cells
Precursor Cells, B-Lymphoid
Single-Cell Analysis
Thymus Gland
Zebrafish

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