Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.
Qin Tang, Sowmya Iyer, Riadh Lobbardi, John C Moore, Huidong Chen, Caleb Lareau, Christine Hebert, McKenzie L Shaw, Cyril Neftel, Mario L Suva, Craig J Ceol, Andre Bernards, Martin Aryee, Luca Pinello, Iain A Drummond, David M Langenau
Author Information
Qin Tang: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA. ORCID
Sowmya Iyer: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
Riadh Lobbardi: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
John C Moore: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA. ORCID
Huidong Chen: Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA.
Caleb Lareau: Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA. ORCID
Christine Hebert: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
McKenzie L Shaw: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
Cyril Neftel: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
Mario L Suva: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
Craig J Ceol: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA. ORCID
Andre Bernards: Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.
Martin Aryee: Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA.
Luca Pinello: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA. ORCID
Iain A Drummond: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
David M Langenau: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA dlangenau@mgh.harvard.edu. ORCID
Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA-protein kinase catalytic subunit (), interleukin-2 receptor γ a (), and double-homozygous-mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish.
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