E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates.

E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates.
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E-钙粘蛋白受加塔-2调节,并标志着小鼠造血祖细胞向嗜碱性粒细胞和肥大细胞命运的早期定型。

DOI:
10.1126/sciimmunol.aba0178
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发表时间:
2021-02-05
期刊:
影响因子:
24.8
通讯作者:
Welner RS
Welner RS
中科院分区:
医学1区
文献类型:
--
作者:
Wanet A;Bassal MA;Patel SB;Marchi F;Mariani SA;Ahmed N;Zhang H;Borchiellini M;Chen S;Zhang J;Di Ruscio A;Miyake K;Tsai M;Paranjape A;Park SY;Karasuyama H;Schroeder T;Dzierzak E;Galli SJ;Tenen DG;Welner RS

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E-钙粘蛋白是一种钙依赖性细胞间粘附分子,因其参与组织形成、上皮细胞行为和肿瘤抑制而被广泛研究。然而,E-cadherin在造血系统中的表达尚未完全阐明。结合单细胞RNA测序分析和免疫表型分析,我们发现,祖细胞表达高水平的E-钙粘蛋白,并包含在粒细胞-单核细胞祖细胞(GMP)部分具有丰富的能力,分化成嗜碱性粒细胞和肥大细胞。重要的是,我们检测到E-钙粘蛋白的表达前,这些谱系的其他报告的标志物的表达定向祖细胞。我们将这种祖细胞命名为pro-BMP(pro-basophil和mast cell progenitor)。使用RNA测序,我们观察到促骨形成蛋白的嗜碱性粒细胞和肥大细胞系的转录启动。我们还表明,加塔-2直接调节E-钙粘蛋白的表达在嗜碱性粒细胞和肥大细胞谱系,从而提供了一个机制之间的联系,这种细胞表面标志物的表达和嗜碱性粒细胞和肥大细胞的命运规范。小鼠造血祖细胞上的E-钙粘蛋白表达标志着它们在早期阶段对嗜碱性粒细胞和肥大细胞命运的承诺。
E-cadherin is a calcium-dependent cell-cell adhesion molecule extensively studied for its involvement in tissue formation, epithelial cell behavior and suppression of cancer. However, E-cadherin expression in the hematopoietic system has not been fully elucidated. Combining single-cell RNA sequencing analyses and immunophenotyping, we revealed that progenitors expressing high levels of E-cadherin and contained within the granulocyte-monocyte progenitors (GMPs) fraction have an enriched capacity to differentiate into basophils and mast cells. Importantly, we detected E-cadherin expression on committed progenitors prior to the expression of other reported markers of these lineages. We named such progenitors pro-BMPs (pro-basophil and mast cell progenitors). Using RNA-sequencing, we observed transcriptional priming of pro-BMPs to the basophil and mast cell lineages. We also showed that GATA-2 directly regulates E-cadherin expression in the basophil and mast cell lineages, thus providing a mechanistic connection between the expression of this cell surface marker and the basophil and mast cell fate specification. E-cadherin expression on mouse hematopoietic progenitors marks their commitment to the basophil and mast cell fates at an early stage.
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