Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis

Abstract

Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship. Here, by evaluating the expression of the ␤7 integrin, a molecule that is required for selective homing of mast cell progenitors (MCPs) to the periphery, we identified bipotent progenitors that are capable of differentiating into either cell type in the mouse spleen. These basophil͞mast cell progenitors (BMCPs) gave rise to basophils and mast cells at the single-cell level and reconstituted both mucosal and connective tissue mast cells. We also identified the basophil progenitor (BaP) and the MCP in the bone marrow and the gastrointestinal mucosa, respectively. We further show that the granulocyte-related transcription factor CCAAT͞ enhancer-binding protein ␣ (C͞EBP␣) plays a primary role in the fate decision of BMCPs, being expressed in BaPs but not in MCPs. Thus, circulating basophils and tissue mast cells share a common developmental stage at which their fate decision might be controlled principally by C͞EBP␣.integrin ͉ progenitor ͉ CCAAT͞enhancer-binding protein

Adipose Tissue as a Dedicated Reservoir of Functional Mast Cell Progenitors

“…1C), with Ct between 24 and 30. In contrast, C/EBPa that controls basophil lineage commitment [26] was faintly expressed by adipose-derived CFC (Ct around 34). Finally, murine mast cell-specific serine protease (pmMCP)-5 mRNA was highly expressed (Ct around 22) in contrast to mMCP-1 (Ct around 31) in adipose-derived CFC and peritoneal cell-derived mast cells (Fig.…”

“…First, adipose-derived CFCs were amplified in liquid medium containing IL-3 and SCF [26] giving rise to a homogeneous population of granular cells showing the same morphology as mast cells obtained in methylcellulose (MGG staining, Supporting Information Fig. 2).…”

Unraveling ALK signaling through phosphoproteomics

“…In all 3 instances, the markers used for depletion are also expressed on the mast cell, the committed mast cell progenitor, and/or the common basophil-mast cell progenitor identified in the spleen of C57BL/6 mice by Arinobu et al 6 Although none of the authors noted a decrease in the mature mast cell number identified in the peritoneal cavity of mice, these cells represent a mature end-stage cell that may not be affected in the limited time frame of these treatments. Nonetheless, this consideration does not diminish other aspects of the study, which demonstrated a life span of basophiles of only about 60 hours and the increased production of these cells in the bone marrow following helminth infection.…”

“…This latter finding is consistent with those of Arinobu et al who, following infection with the helminth, Trichinella spiralis, also noted increased basophil production by the bone marrow and increased numbers of the common basophil-mast cell progenitor in the spleen. 6 Importantly, Ohnmacht and Voehringer then addressed whether the increased numbers associated with TH-2 inflammation was the result of increased production, increased survival, or both. The increased survival as a consequence of the cytokines generated by TH-2 inflammation, particularly IL-3, has been shown in vitro using human basophils 7 and was recently further studied by Didichenko et al, who found this is mediated by IL-3 activation of PIM-1.…”

“…Advances in liquid chromatography-tandem mass spectrometry-driven proteomics have shifted the paradigm of translational cancer research that enables fast and reliable large scale study of proteins involved in many disease models. 4 It follows that identifying the ALK-regulated proteome 5,6 and phosphoproteome would lead to key insights into the signaling pathways important for the pathogenesis of ALCL.…”