Hematopoietic progenitor cell lines with myeloid and lymphoid potential

Redecke, Vanessa; Wu, Ruiqiong; Zhou, Jingran; Finkelstein, David; Chaturvedi, V. N.; High, Anthony A.; Häcker, H.

doi:10.1038/nmeth.2510

Cited by 127 publications

(192 citation statements)

References 40 publications

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“…To further explore the role of LAR phosphatases in murine pDCs, we utilized a conditionally transformed progenitor cell line HoxB8-FL that can be differentiated into functional pDCs (Redecke et al, 2013). We derived HoxB8-FL cells expressing yellow fluorescent protein (YFP) reporter from the IFN-β-encoding Ifnb gene and differentiating into pDCs with >90% efficiency (Figure 5A).…”

Section: Resultsmentioning

confidence: 99%

Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

et al. 2015

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SUMMARY Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system, receptor protein tyrosine phosphatase sigma (PTPRS) is expressed specifically on pDCs. Surface PTPRS was rapidly downregulated after pDC activation, and only PTPRS– pDCs produced IFN-α. Antibody-mediated PTPRS crosslinking inhibited pDC activation, whereas PTPRS knockdown enhanced IFN response in a pDC cell line. Similarly, murine Ptprs and the homologous receptor phosphatase Ptprf were specifically co-expressed in murine pDCs. Haplodeficiency or DC-specific deletion of Ptprs on Ptprf-deficient background were associated with enhanced IFN response of pDCs, leukocyte infiltration in the intestine and mild colitis. Thus, PTPRS represents an evolutionarily conserved pDC-specific inhibitory receptor, and is required to prevent spontaneous IFN production and immune-mediated intestinal inflammation.

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Section: Resultsmentioning

confidence: 99%

Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

et al. 2015

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“…5B). The HoxB8-FL cell line was recently reported to have both myeloid and lymphoid potential (29). We therefore also generated expression profiles for 107 HoxB8-FL single cells, which, when projected onto the diffusion plot, confirmed that the HoxB8-FL expression state resembles that of primary bone marrow cells from the LMPP trajectory.…”

Section: Resultsmentioning

confidence: 63%

Reconstructing blood stem cell regulatory network models from single-cell molecular profiles

Hamey

Nestorowa

Kinston

et al. 2017

Experimental Hematology

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Adult blood contains a mixture of mature cell types, each with specialized functions. Single hematopoietic stem cells (HSCs) have been functionally shown to generate all mature cell types for the lifetime of the organism. Differentiation of HSCs toward alternative lineages must be balanced at the population level by the fate decisions made by individual cells. Transcription factors play a key role in regulating these decisions and operate within organized regulatory programs that can be modeled as transcriptional regulatory networks. As dysregulation of single HSC fate decisions is linked to fatal malignancies such as leukemia, it is important to understand how these decisions are controlled on a cell-bycell basis. Here we developed and applied a network inference method, exploiting the ability to infer dynamic information from single-cell snapshot expression data based on expression profiles of 48 genes in 2,167 blood stem and progenitor cells. This approach allowed us to infer transcriptional regulatory network models that recapitulated differentiation of HSCs into progenitor cell types, focusing on trajectories toward megakaryocyteerythrocyte progenitors and lymphoid-primed multipotent progenitors. By comparing these two models, we identified and subsequently experimentally validated a difference in the regulation of nuclear factor, erythroid 2 (Nfe2) and core-binding factor, runt domain, alpha subunit 2, translocated to, 3 homolog (Cbfa2t3h) by the transcription factor Gata2. Our approach confirms known aspects of hematopoiesis, provides hypotheses about regulation of HSC differentiation, and is widely applicable to other hierarchical biological systems to uncover regulatory relationships.gene regulatory networks | hematopoiesis | single cell | Boolean network | stem progenitor cells

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“…In addition to GATA1 and CEPBA, recovered for erythroid lineage and myeloid lineages, respectively (Fig. 2c), along the erythroid cell differentiation trajectory, we uncovered several additional potential regulators for HSCs (ATF3 34 , HOXB8 35 ) and MEPs (LMO2 36 ,TAL1 30 ) (Supplementary Fig.15 ).…”

Section: Supplementary Figure 15 Stream Automatically Discovers Impormentioning

confidence: 95%

STREAM: Single-cell Trajectories Reconstruction, Exploration And Mapping of omics data

Chen

Albergante

Hsu

et al. 2018

Preprint

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Single-cell transcriptomic assays have enabled the de novo reconstruction of lineage differentiation trajectories, along with the characterization of cellular heterogeneity and state transitions. Several methods have been developed for reconstructing developmental trajectories from single-cell transcriptomic data, but efforts on analyzing single-cell epigenomic data and on trajectory visualization remain limited. Here we present STREAM, an interactive pipeline capable of disentangling and visualizing complex branching trajectories from both single-cell transcriptomic and epigenomic data.

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Hematopoietic progenitor cell lines with myeloid and lymphoid potential

Cited by 127 publications

References 40 publications

Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

Reconstructing blood stem cell regulatory network models from single-cell molecular profiles

STREAM: Single-cell Trajectories Reconstruction, Exploration And Mapping of omics data

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