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Cell Rep. 2016 Feb 2;14(4):966-977. doi: 10.1016/j.celrep.2015.12.082. Epub 2016 Jan 21.

Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells.

Author information

1
Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
2
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
3
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK.
4
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK.
5
Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; Department of Human Genetics, University of Leuven, Leuven 3000, Belgium.
6
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK. Electronic address: as889@cam.ac.uk.

Abstract

The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment.

PMID:
26804912
PMCID:
PMC4742565
DOI:
10.1016/j.celrep.2015.12.082
[Indexed for MEDLINE]
Free PMC Article

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