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J Exp Med. 2017 Oct 2;214(10):2875-2887. doi: 10.1084/jem.20170976. Epub 2017 Sep 6.

Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.

Tang Q1,2,3,4, Iyer S1, Lobbardi R1,2,3,4, Moore JC1,2,3,4, Chen H5,6,7, Lareau C8,5, Hebert C1,9, Shaw ML1,9, Neftel C1,9, Suva ML1,9, Ceol CJ10, Bernards A2, Aryee M8,5, Pinello L1,2, Drummond IA11, Langenau DM12,2,3,4.

Author information

1
Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
2
Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.
3
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.
4
Harvard Stem Cell Institute, Harvard University, Cambridge, MA.
5
Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA.
6
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
7
Department of Computer Science and Technology, Tongji University, Shanghai, China.
8
Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA.
9
Broad Institute, Cambridge, MA.
10
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA.
11
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
12
Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA dlangenau@mgh.harvard.edu.

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 (prkdc), interleukin-2 receptor γ a (il2rga), 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.

PMID:
28878000
PMCID:
PMC5626406
DOI:
10.1084/jem.20170976
[Indexed for MEDLINE]
Free PMC Article

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