The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways
The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways
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DOI：
10.1182/blood-2007-02-071613
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发表时间：
2007-11-15
期刊：
影响因子：
20.3
通讯作者：
Akashi, Koichi
中科院分区：
文献类型：
--
作者：
Ishikawa, Fumihiko;Niiro, Hiroaki;Akashi, Koichi
两种不同的树突状细胞 (DC) 亚群，即常规 DC (cDC) 和浆细胞样 DC (pDC)，已被证明在小鼠造血过程中通过骨髓或淋巴途径发育。然而，“骨髓”和“淋巴”DC 的谱系特异性表型或功能仍然难以捉摸。此外，由于缺乏适合分析人类干细胞和祖细胞分化的测定系统，这种分析在人类中尤其困难。在这里，我们使用高效的异种移植模型，广泛分析了人类 DC 的起源和分子特征。将纯化的人共同骨髓祖细胞（CMP）和共同淋巴祖细胞（CLP）静脉内移植到非肥胖糖尿病-严重联合免疫缺陷（NOD-scid）/lL2r γ（无效）新生小鼠中。 CMP 和 CLP 在异种宿主中表现出显着的扩增，并且人类 cDC 和 pDC 后代是可分离的。引人注目的是，每个人类 DC 亚群都具有无法区分的表面表型和基因转录本的表达模式，无论其 CMP 或 CLP 来源如何，甚至在全基因组水平上也是如此。因此，cDC和pDC通常在细胞定型为人类造血过程中的骨髓或淋巴谱系后发育，而无论其谱系起源如何，它们的转录特征都得到很好的保存。我们建议人类树突状细胞使用独特且灵活的发育程序，不能归类为传统的骨髓或淋巴途径。
Two distinct dendritic cell (DC) subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have been shown to develop via either the myeloid or the lymphoid pathway in murine hematopolesis. Lineage-specific phenotypes or functions of "myeloid" and "lymphoid" DCs, however, still remain elusive. Furthermore, such analysis has been particularly difficult in humans, due to lack of an assay system appropriate for the analysis of human stem and progenitor cell differentiation. Here, using a highly efficient xenotransplantation model, we extensively analyze the origin and the molecular signature of human DCs. Purified human common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs) were intravenously transplanted into nonobese diabetic-severe combined immunodeficiency (NOD-scid)/lL2r gamma(null) newborn mice. CMPs and CLPs displayed significant expansion in the xenogeneic host, and human cDC and pDC progeny were isolatable. Strikingly, each human DC subset possessed indistinguishable expression patterns of surface phenotype and gene transcripts regardless of their CMP or CLP origin, even at the genome-wide level. Thus, cDC and pDC normally develop after cells have committed to the myeloid or the lymphoid lineage in human hematopoiesis, while their transcriptional signatures are well preserved irrespective of their lineage origin. We propose that human DCs use unique and flexible developmental programs that cannot be categorized into the conventional myeloid or lymphoid pathway.