Clinical Medicine Postgraduate Programme, College of Medicine, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, Brazil.
Cytometry Service, Institute of Paediatrics and Puericulture Martagão Gesteira (IPPMG), UFRJ, Rio de Janeiro, Brazil.
Br J Haematol. 2017 Feb;176(3):464-474. doi: 10.1111/bjh.14467. Epub 2017 Jan 12.
Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis. Five distinct maturation-associated stages of monocytic precursors were identified and isolated from (fresh) normal human BM through fluorescence-activated cell sorting, and the gene expression profile (GEP) of each monocytic precursor subset was analysed by DNA-oligonucleotide microarrays. Overall, >6000 genes (18% of the genes investigated) were expressed in ≥1 stage of BM monopoiesis at stable or variable amounts, showing early decrease in cell proliferation with increased levels of expression of genes linked with cell differentiation. The here-defined GEP of normal human BM monopoiesis might contribute to better understand monocytic differentiation and the identification of novel monocytic candidate markers, while also providing a frame of reference for the study of monocytic maturation in both neoplastic and non-neoplastic disease conditions involving monocytic precursor cells.
人类单核细胞生成是一个紧密协调的过程，起始于骨髓（BM）造血干细胞（HSC）区室，并导致循环血液成熟单核细胞的产生。尽管成熟的单核细胞/巨噬细胞在正常或炎症条件下已经得到了广泛研究，但由于正常人类 BM 中单核细胞前体的频率较低，单核细胞生成仅在体外和体内动物模型中进行了评估。在这里，我们研究了正常人类 BM 单核细胞生成过程中的转录谱。通过荧光激活细胞分选，从（新鲜）正常人类 BM 中鉴定和分离出五个不同的与成熟相关的单核细胞前体阶段，并通过 DNA-寡核苷酸微阵列分析每个单核细胞前体亚群的基因表达谱（GEP）。总体而言，≥1 个 BM 单核细胞生成阶段稳定或可变地表达了>6000 个基因（研究基因的 18%），显示出细胞增殖的早期减少，同时与细胞分化相关的基因表达水平增加。这里定义的正常人类 BM 单核细胞生成的 GEP 可能有助于更好地理解单核细胞分化和新的单核细胞候选标志物的鉴定，同时也为研究涉及单核细胞前体细胞的肿瘤性和非肿瘤性疾病条件下的单核细胞成熟提供了参考框架。
