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The Journal of experimental medicine
Oct 02, 2017;214 (10): 2875-2887.

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
  1. Qin Tang: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA. ORCID
  2. Sowmya Iyer: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
  3. Riadh Lobbardi: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
  4. John C Moore: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA. ORCID
  5. Huidong Chen: Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA.
  6. Caleb Lareau: Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA. ORCID
  7. Christine Hebert: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
  8. McKenzie L Shaw: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
  9. Cyril Neftel: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
  10. Mario L Suva: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
  11. Craig J Ceol: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA. ORCID
  12. Andre Bernards: Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.
  13. Martin Aryee: Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA.
  14. Luca Pinello: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA. ORCID
  15. Iain A Drummond: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
  16. David M Langenau: Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA dlangenau@mgh.harvard.edu. ORCID
PMID: 28878000 DOI: 10.1084/jem.20170976

Abstract

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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Grants

  1. R01 AR063850/NIAMS NIH HHS
  2. R01 DK053093/NIDDK NIH HHS
  3. R24 OD016761/NIH HHS
  4. UH3 DK107372/NIDDK NIH HHS

MeSH Term

Animals
Animals, Genetically Modified
Cell Lineage
Gene Expression Profiling
Hematopoiesis, Extramedullary
Hematopoietic Stem Cells
Kidney
RNA
Sequence Analysis, RNA
Zebrafish

Chemicals

RNA
Journal Article

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