Trim27 confers myeloid hematopoiesis competitiveness by up-regulating myeloid master genes

Abstract

Trim27 (Zinc finger protein RFP) is a potential regulator of hematopoietic stem cells (HSC), yet its role in hematopoiesis remains elusive. Here, we investigated the roles of Trim27 in hematopoiesis by enforcing its expression in mouse and human hematopoietic stem and progenitor cells (HSPC). Ectopic expression of Trim27 in mouse fetal liver (FL) HSPC confers repopulating advantage with myeloid dominance. However, the number of HSC from Trim27 group was comparable with empty vector control group, indicating that overexpression of Trim27 unlikely expanded HSC. Transcriptome analysis of Trim27-overexpressing myeloid progenitor cells (MP) indicated that Trim27 up-regulated essential regulators of myelopoiesis, including Spi1 and Cebpg, up-regulated myeloid proliferation-related signaling genes Nras, Runx1, and Cbfb, up-regulated JAK/STAT signaling inhibitors Socs2, Socs3, and Cish, and up-regulated myeloid maturation-related genes Adam8 and Dek. Moreover, the myeloproliferative advantage caused by overexpressing Trim27/TRIM27 is conserved between mouse and human hematopoiesis. To our knowledge, this is the first study showing that Trim27 confers competitive hematopoiesis by promoting myeloid bias differentiation of HSPC, but not by expanding HSC.

Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model

“…To identify the primary neutrophil commitment regulatory genes, we first cloned cDNAs of CEBPE, LRG1, PRTN3 and CLEC11A into PCCL-desRed or PCCL-EGFP overexpression vectors [ 27 ], and the shRNA target sequences of these genes into plKO.1-GFP vectors. Both overexpression and shRNA knockdown experiments indicated that CEBPE, PRTN3, LRG1, and CLEC11A did not affect human neutrophil differentiation ( Supplementary Fig.…”

“…The cDNA of CLEC11A (NM_002975), LRG1 (NM_052 972), PRTN3 (NM_002777), CEBPE (NM_001805), CEBPE-M (U80982.1), XRCC3, TMEM176B, PBX3, MDM1, MDB3, HMGA1, ELK1, and short-ELK1 from the dsDNA of neutrophil biased progenitors was cloned into the PCCL-MND-PGK-dsRed or PCCL-MND-PGK-EGFP lentiviral vector as previously reported [ 27 ]. Knocking down the target genes in CD34 + cells was mediated by short hairpin RNA (shRNA).…”

“…Lentiviral preparation and transduction of CD34 + HSPCs were performed as we previously described [ 27 ]. The neutrophil and monocyte differentiation potential of total transduced cells or sorted transduced cells (GFP + CD115 – CD371 + gated CD34 + CD15 – , CD34 mid CD15 mid , CD34 low/- CD15 + ) was analyzed by culturing in IMDM plus 10% FBS containing 7 cytokines (10 ng/mL SCF, 10 ng/mL FLT3L, 10 ng/mL TPO, 10 ng/mL IL-3, 10 ng/mL IL-6, 10 ng/mL GM-CSF and 20 ng/mL G-CSF) for 7–14 days.…”

Synergy of NUP98-HOXA10 Fusion Gene and NrasG12D Mutation Preserves the Stemness of Hematopoietic Stem Cells on Culture Condition

“…In addition, cell apoptosis related genes Hmgb2 [18], Ccnb1 [19], Aurka [20], Rrm1 [21], Tpx2 [22], Prc1 [23], and Pbk [24] were upregulated in NV HSC while downregulated in NA10hd HSC (Figure 5D). Genes that regulate the hematopoietic stem cell activity [25,26,27,28] including Hoxa10 , Hoxa7 , Hoxa9 , Ski , Prdm16 , Vps72 , Hoxb4 , and Akt1 were up-regulated in NA10hd HSC, while only Trim27 and Smarcc1 were up-regulated in NV HSC (Figure S3). Collectively, the above results demonstrate that NA10hd and NV conferred competitiveness on HSC by distinct mechanisms.…”

Weighted gene co-expression network analysis identifies key hub genes and pathways in acute myeloid leukemia

“…A study by Ma et al (2019) revealed that overexpression of TRIM27 suppresses apoptosis of esophagus cancer cells and increased their glucose uptake. Transcriptome analysis of Trim27-overexpressing myeloid progenitor cells indicated that it increased the expression of myelopoiesis regulators, myeloid proliferation-related signaling genes, and myeloid maturationrelated genes (Wang et al, 2018). MEF2C, a TF, is encoded by the member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins and is known to play a role in myogenesis.…”