Central gene transcriptional regulatory networks shaping monocyte development in bone marrow

Abstract

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.

Trappc1 intrinsically prevents ferroptosis of naive T cells to avoid spontaneous autoinflammatory disease in mice

“…We further analyzed the protein processing in ER pathway‐related genes and found that the commonly upregulated genes in Trappc1 cKO naive CD4 + and CD8 + T cells were mainly enriched in ER stress‐related parts. By using gene set enrichment analysis (GSEA) software [38], we found that the positive regulation of response to ER stress pathway was significantly enriched in Trappc1 cKO naive CD4 + and CD8 + T cells (Fig. 3E).…”

“…The total RNA of the sorted naive CD4 + T cells and naive CD8 + T cells were extracted using TRIzol reagent (Thermo Fisher, 15596018) and sequencing was done by the Annoroad Gene Technology Co., Ltd. (Beijing). Differential expressed genes were carried out by DEseq2 software [38]. KEGG pathway enrichment was performed by KOBAS 3.0.28 (http://kobas.cbi.pku.edu.cn/) [37,59].…”

mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway

“… 62 https://cytoscape.org/ STRING11.5 This paper https://cn.string-db.org/cgi/input?sessionId=brxHAcCk07dk&input_page_show_search=on GSEA_4.0.3 Zhang et al. 7 , 63 https://www.gsea-msigdb.org/gsea/index.jsp DESeq23.17 Wang et al. 64 Lei et al.…”

“… 2 , 3 Some early progenitors will lose multipotency to adopt a particular fate, while others continue to undergo lineage commitment and differentiation under elegant regulation by transcriptional profiles, growth factors, and cytokines/chemokines. 4 , 5 , 6 , 7 Myeloid hematopoiesis is a finely controlled consecutive developmental process, and the intrinsic molecular mechanisms regulating myelopoiesis remain to be studied. Thus, exploring the carefully regulated molecular network underlying the differentiation of myeloid progenitors into downstream cell subsets is critical to our understanding of the finely orchestrated process of myeloid development during homeostasis and myelopoiesis emergency.…”

Insight into the role of IRF7 in skin and connective tissue diseases

“…112 RNA sequencing data suggested that IRF7 may regulate the transition of granulocyte-monocyte progenitors (GMPs) into monocytes in both mice and humans. 113 Moreover, IRF7 is activated in inflammatory monocytes and bone marrow-derived macrophages by TLR2. 114 IRF7 is a key regulator in directing the transformation of monocytes into macrophages.…”