State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Oct 11;13:1011279. doi: 10.3389/fimmu.2022.1011279. eCollection 2022.
The development of monocytes in bone marrow is a complex process with multiple steps. We used RNA-seq data to analyze the transcriptome profiles in developing stages of monocytes, including hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), and monocytes. We found that genes related to potassium and other cation transmembrane activities and ion binding were upregulated during the differentiation of HSCs into CMPs. Protein transport and membrane surface functional molecules were significantly upregulated in the GMP stage. The CD42RAC and proteasome pathways are significantly upregulated during the development of HSCs into monocytes. Transcription factors Ank1, Runx2, Hmga2, Klf1, Nfia, and Bmyc were upregulated during the differentiation of HSCs into CMPs; Gfi1 and Hmgn2 were highly expressed during the differentiation of CMPs into GMPs; Seventeen transcription factors including Foxo1, Cdkn2d, Foxo3, Ep300, Pias1, Nfkb1, Creb1, Bcl6, Ppp3cb, Stat5b, Nfatc4, Mef2a, Stat6, Ifnar2, Irf7, Irf5, and Cebpb were identified as potentially involved in the development of GMPs into monocytes in mice and humans. In metabolism pathway regulation, HSCs have high glucose, lipid, and nucleic acid metabolism activities; CMPs mainly up regulate the TCA cycle related genes; and GMPs have extremely active metabolisms, with significantly elevated pentose phosphate pathway, TCA cycle, histidine metabolism, and purine metabolism. In the monocyte phase, the tricarboxylic acid (TCA) cycle is reduced, and the anaerobic glycolysis process becomes dominated. Overall, our studies offer the kinetics and maps of gene transcriptional expressions and cell metabolisms during monocyte development in bone marrow.
单核细胞在骨髓中的发育是一个多步骤的复杂过程。我们使用 RNA-seq 数据来分析单核细胞发育阶段的转录组谱，包括造血干细胞（HSCs）、共同髓系祖细胞（CMPs）、粒细胞-单核细胞祖细胞（GMPs）和单核细胞。我们发现，在 HSCs 分化为 CMPs 的过程中，与钾和其他阳离子跨膜活性以及离子结合相关的基因上调。在 GMP 阶段，蛋白质转运和膜表面功能分子显著上调。在 HSCs 向单核细胞分化过程中，CD42RAC 和蛋白酶体途径显著上调。转录因子 Ank1、Runx2、Hmga2、Klf1、Nfia 和 Bmyc 在 HSCs 分化为 CMPs 的过程中上调；Gfi1 和 Hmgn2 在 CMPs 分化为 GMPs 的过程中高表达；在小鼠和人类中，有 17 个转录因子（包括 Foxo1、Cdkn2d、Foxo3、Ep300、Pias1、Nfkb1、Creb1、Bcl6、Ppp3cb、Stat5b、Nfatc4、Mef2a、Stat6、Ifnar2、IrF7、IrF5 和 Cebpb）被鉴定为可能参与 GMP 向单核细胞的发育。在代谢途径调控方面，HSCs 具有高葡萄糖、脂质和核酸代谢活性；CMPs 主要上调 TCA 循环相关基因；而 GMPs 具有极其活跃的代谢，戊糖磷酸途径、TCA 循环、组氨酸代谢和嘌呤代谢显著升高。在单核细胞阶段，三羧酸（TCA）循环减少，无氧糖酵解过程占主导地位。总的来说，我们的研究提供了骨髓中单核细胞发育过程中基因转录表达和细胞代谢的动力学和图谱。
