Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish

Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

“…To test whether D. rerio and human pre-B ALL share similar gene expression, we next defined GEPs in a new cohort of animals, quantifying 96 transcripts that distinguish B/T/NK cells, lymphoblasts, and precursor populations (genelist in Table S1) (29, 30). We FACS-purified 8 pre-B ALL, 4 T-ALL, and 2 ALL from a mixed-ALL fish (Fig.…”

Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types

“…In addition to nitr and dicp genes, the second cluster expressed NK lysins with high specificity (in particular nk-lysin tandem duplicate 2 and 4) (see Fig. 3), which have been recently proposed to mark a distinct population of NK-like cells and are up-regulated in recombination activating gene 1-deficient (rag1 −/− ) zebrafish (Pereiro et al 2015;Moore et al 2016). This further supported our hypothesis that cells in this cluster mainly correspond to a zebrafish equivalent of mammalian NK cells.…”

“…To our knowledge, this is the first study to characterize T and NK cells at the whole-transcriptome level in a nonmammalian species and one of the first studies to analyze NK cells' gene expression at the single-cell level (for scRNA-seq of human NK cells, see Björklund et al 2016; for qPCR analysis of Tg(lck:GFP) zebrafish single cells, see Moore et al 2016). We confirmed cell-type-specific expression of expected zebrafish T-and NK-cell genes and predicted new markers of these two cell types.…”

“…NK-like cells have been identified in nonmammalian species such as chicken (Jansen et al 2010), Xenopus (Horton et al 1996), and catfish, where spontaneous killing of allogeneic cells by non-TCR expressing cytotoxic cells was demonstrated (Shen et al 2004;Yoder 2004). A recent study using single-cell qPCR based on known markers of blood cell lineages revealed the presence of a small population of immune cells in zebrafish, which were proposed to represent putative NK-like cells based on expression of NK-lysin genes (Moore et al 2016). The identification of membrane receptors with similar genomic organization as the KIR genes in humans provided additional evidence for the existence of NK cells in fish species.…”

Single-cell molecular analysis defines therapy response and immunophenotype of stem cell subpopulations in CML

“…[17][18][19][20][21][22][23] In leukemia, single-cell methods additionally offer the opportunity to discriminate between leukemic and healthy cells, thereby allowing for specific characterization of the infrequent residual LSC population even months into treatment. Here we have dissected the heterogeneity of the CML LSC population both at diagnosis and following 3 months of TKI treatment.…”