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A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice.

TitleA single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsDahlin, J. S., Hamey F. K., Pijuan-Sala B., Shepherd M., W Y Lau W., Nestorowa S., Weinreb C., Wolock S., Hannah R., Diamanti E., Kent D. G., Göttgens B., & Wilson N. K.
JournalBlood
Volume131
Issue21
Paginatione1-e11
Date Published2018 May 24
ISSN1528-0020
Abstract

Hematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system, and their dysregulation causes a multitude of diseases. However, the differentiation journeys toward specific hematopoietic lineages remain ill defined, and system-wide disease interpretation remains challenging. Here, we have profiled 44 802 mouse bone marrow HSPCs using single-cell RNA sequencing to provide a comprehensive transcriptional landscape with entry points to 8 different blood lineages (lymphoid, megakaryocyte, erythroid, neutrophil, monocyte, eosinophil, mast cell, and basophil progenitors). We identified a common basophil/mast cell bone marrow progenitor and characterized its molecular profile at the single-cell level. Transcriptional profiling of 13 815 HSPCs from the c-Kit mutant (W/W) mouse model revealed the absence of a distinct mast cell lineage entry point, together with global shifts in cell type abundance. Proliferative defects were accompanied by reduced expression. Potential compensatory processes included upregulation of the integrated stress response pathway and downregulation of proapoptotic gene expression in erythroid progenitors, thus providing a template of how large-scale single-cell transcriptomic studies can bridge between molecular phenotypes and quantitative population changes.

DOI10.1182/blood-2017-12-821413
Alternate JournalBlood
PubMed ID29588278
PubMed Central IDPMC5969381
Grant List / / Wellcome Trust / United Kingdom
R24 DK106766 / DK / NIDDK NIH HHS / United States

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