Transcriptional regulation of mast cell and basophil lineage commitment

Huang, Hua; Li, Yapeng; Liu, Bing

doi:10.1007/s00281-016-0562-4

Cited by 30 publications

(34 citation statements)

References 84 publications

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“…GMP then led to classical monocytes that further led to myeloid dendritic cells on one branch and to cells labeled as intermediate monocytes on another branch. UMAP linked basophils to a population of Lin − cKit + Sca1 − CD34 + FcγRII/III + FcεRIα + cells, consistently with a previously-described phenotype for committed basophil progenitors [10]. These putative progenitors appeared closer to CMP than GMP, a topic that is still intensely debated.…”

Section: Umap Better Represents the Multi-branched Trajectory Of Hemasupporting

confidence: 79%

Evaluation of UMAP as an alternative to t-SNE for single-cell data

Becht

Dutertre

Kwok

et al. 2018

Preprint

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Uniform Manifold Approximation and Projection (UMAP) is a recently-published non-linear dimensionality reduction technique. Another such algorithm, t-SNE, has been the default method for such task in the past years. Herein we comment on the usefulness of UMAP high-dimensional cytometry and single-cell RNA sequencing, notably highlighting faster runtime and consistency, meaningful organization of cell clusters and preservation of continuums in UMAP compared to t-SNE. IntroductionThe last decades have witnessed a large increment in the number of parameters analysed in single cell cytometry studies. It currently reaches around 20 for flow-cytometry, 40 for masscytometry, and more than 20,000 in single-cell RNA-sequencing. In this context, dimensionality reduction techniques have been pivotal in enabling researchers to visualize high-dimensional data. While principal component analysis has historically been the main technique used for dimensionality reduction (DR), the recent years have highlighted the importance of non-linear DR techniques to avoid overcrowding issues. [3]). t-SNE is currently the most commonly-used technique and is efficient at highlighting local structure in the data, which for cytometry notably translates to the representation of cell populations as distinct clusters. t-SNE however suffers from limitations such as loss of large-scale information (the inter-cluster relationships), slow computation time and inability to meaningfully represent very large datasets [4]. A new algorithm, called Uniform Manifold Approximation and Projection (UMAP) has been recently published by McInnes and Healy[5]. They claim that compared to t-SNE it preserves as much of the local and more of the global data structure, with a shorter runtime. Since t-SNE has been extremely prevalent in the field of cytometry broadly encompassing flow and mass-cytometry as well as singlecell RNA-sequencing (scRNAseq), we tested these claims on well-characterized single-cell datasets [6][7][8]. We confirm that UMAP is an order of magnitude faster than t-SNE. In addition to this straightforward advantage, we argue that UMAP is not only able to create informative clusters, but is also able to organize these clusters in a meaningful way. We illustrate these claims by showing that UMAP can order clusters from T and NK cells from 8 human organs [7] in a way that both identifies major cell lineages but also a common axis that broadly recapitulates their differentiation stages. We also show that UMAP allows for an easier visualization of multibranched cellular trajectories by using a mass-cytometry[6] and a scRNAseq[8] datasets both recapitulating hematopoiesis.

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Section: Umap Better Represents the Multi-branched Trajectory Of Hemasupporting

confidence: 79%

Evaluation of UMAP as an alternative to t-SNE for single-cell data

Becht

Dutertre

Kwok

et al. 2018

Preprint

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“…However, the developmental relationship between basophils, mast cells, and other hematopoietic cells remains to be fully elucidated. 1 Several studies suggest that human basophils develop from common basophil-eosinophil progenitors (Fig 1). 2,3 Hybridtype cells possessing both basophil and eosinophil phenotypes have been detected in the bone marrow, cord blood, and peripheral blood of patients with myeloid leukemia.…”

Section: Ontogeny Of Basophilsmentioning

confidence: 99%

“…4,5 In mice multiple differential pathways that give rise to basophils might exist (Fig 1). 1 A recent study identified a novel population of common basophil-mast cell progenitors in mouse bone marrow. 6 A series of transcription factors are involved in the differentiation and commitment of basophils and mast cells.…”

Section: Ontogeny Of Basophilsmentioning

confidence: 99%

Multifaceted roles of basophils in health and disease

Karasuyama

Miyake

Yoshikawa

et al. 2018

Journal of Allergy and Clinical Immunology

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Until recently, basophils had often been neglected in immunologic studies because of their minority status among immune cells or confused with tissue-resident mast cells because of some phenotypic similarities between them in spite of different anatomic localization. It is now appreciated that basophils and mast cells are distinct cell lineages and that basophils play important and nonredundant roles distinct from those played by mast cells. On the one hand, basophils contribute beneficially to protective immunity, particularly against parasitic infections. On the other hand, basophils are involved in the development of various disorders, including allergy and autoimmune disease. Basophils interact with other immune cells and nonhematopoietic cells through cell-to-cell contact or basophil-derived factors, such as cytokines and proteases, contributing to the regulation of immune and allergic responses. In this review article we highlight recent advances in our understanding of basophil pathophysiology in human subjects and animal models by consolidating research findings reported during the past 5 years. Further studies on basophils and their products will help identify suitable targets for novel therapeutics in allergy and effective vaccines against parasitic infection.

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“…[1][2][3] It is now well accepted that basophils and mast cells are distinct cell lineages. 4 Recent studies have identified crucial roles for basophils, distinct from those played by mast cells, in immune responses including allergy and protective immunity. [5][6][7][8] In response to various stimuli, basophils can readily secrete large quantities of the cytokine interleukin-4 (IL-4), which plays a versatile role in immunity through regulating other cells.…”

Section: Introductionmentioning

confidence: 99%

Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice

Iki

Tanaka

Hayato

et al. 2016

Blood

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Recent studies have identified nonredundant roles for basophils in immune responses including allergy and protective immunity. It is well known that activated basophils release granule contents such as histamine and proteases as do mast cells. However, the functional significance of basophil-derived proteases remains poorly understood in contrast to those released from mast cells. For this study we generated a line of knockout (KO) mice deficient for mouse mast cell protease-11 (mMCP-11) that is preferentially expressed by basophils rather than mast cells. In spite of normal development of basophils, the mMCP-11-deficient mice showed amelioration of immunoglobulin E-mediated chronic allergic inflammation (IgE-CAI), with reduction of cutaneous swelling, microvascular permeability, and leukocyte infiltration in the skin lesion, when KO mice were compared with wild-type mice. Repeated administration of recombinant mMCP-11 in the skin induced infiltration of leukocytes, including basophils, in a tryptase activity-dependent manner. The transwell migration assay in vitro suggested that mMCP-11-mediated proteolytic products of serum protein promoted migration of basophils, eosinophils, and macrophages via 1 or more G protein-coupled receptors. Thus, basophil tryptase mMCP-11 is a crucial effector molecule for the induction of IgE-CAI. This is the first demonstration that the basophil-derived protease plays a significant role in vivo.

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Transcriptional regulation of mast cell and basophil lineage commitment

Cited by 30 publications

References 84 publications

Evaluation of UMAP as an alternative to t-SNE for single-cell data

Evaluation of UMAP as an alternative to t-SNE for single-cell data

Multifaceted roles of basophils in health and disease

Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice

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