Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis
Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis
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DOI：
10.1073/pnas.0509148102
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发表时间：
2005-12-13
影响因子：
11.1
通讯作者：
Akashi, K
中科院分区：
文献类型：
--
作者：
Arinobu, Y;Iwasaki, H;Akashi, K
嗜碱性粒细胞和肥大细胞选择性地具有高亲和力IgE受体，并介导一系列适应性和先天性免疫应答，它们之间的发育关系尚不清楚。在这里，通过评估β 7整联蛋白的表达，一种选择性地将肥大祖细胞（MCP）归巢到外周所需的分子，我们鉴定了能够在小鼠脾脏中分化成任一细胞类型的双能祖细胞。这些嗜碱性粒细胞/肥大细胞祖细胞（BMCP）在单细胞水平产生嗜碱性粒细胞和肥大细胞，并重建粘膜和结缔组织肥大细胞。我们还确定了嗜碱性祖细胞（球）和MCP在骨髓和胃肠道粘膜，分别。我们进一步表明，粒细胞相关转录因子CCAAT/增强子结合蛋白α（C/EBP α）在BMCP的命运决定中起着主要作用，在BaPs中表达，但不在MCP中表达。因此，循环嗜碱性粒细胞和组织肥大细胞有一个共同的发育阶段，在这个阶段，它们的命运决定可能主要由C/EBP α控制。
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 beta 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 basophil/mast 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 (Ball) and the MCP in the bone marrow and the gastrointestinal mucosa, respectively. We further show that the granulocyte-related transcription factor CCAAT/enhancer-binding protein alpha (C/EBP alpha) 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 C/EBP alpha.