Document Type
Article
Publication Date
7-1-2019
Abstract
Tumor necrosis factor alpha (TNF-α) is a potent cytokine involved in systemic inflammation and immune modulation. Signaling responses that involve TNF-α are context dependent and capable of stimulating pathways promoting both cell death and survival. TNF-α treatment has been investigated as part of a combined therapy for acute myeloid leukemia due to its modifying effects on all-trans retinoic acid (ATRA) mediated differentiation into granulocytes. To investigate the interaction between cellular differentiation and TNF-α, we performed RNA-sequencing on two forms of the human HL-60/S4 promyelocytic leukemia cell line treated with TNF-α. The ATRA-differentiated granulocytic form of HL-60/S4 cells had an enhanced transcriptional response to TNF-α treatment compared to the undifferentiated promyelocytes. The observed TNF-α responses included differential expression of cell cycle gene sets, which were generally upregulated in TNF-α treated promyelocytes, and downregulated in TNF-α treated granulocytes. This is consistent with TNF-α induced cell cycle repression in granulocytes and cell cycle progression in promyelocytes. Moreover, we found evidence that TNF-α treatment of granulocytes shifts the transcriptome toward that of a macrophage. We conclude that TNF-α treatment promotes a divergent transcriptional program in promyelocytes and granulocytes. TNF-α promotes cell cycle associated gene expression in promyelocytes. In contrast, TNF-α stimulated granulocytes have reduced cell cycle gene expression, and a macrophage-like transcriptional program.
Recommended Citation
Jacobson, Elsie C.; Jain, Lekha; Vickers, Mark H.; Olins, Ada L.; Olins, Donald E.; Perry, Jo K.; and O'Sullivan, Justin M., "TNF-α Differentially Regulates Cell Cycle Genes In Promyelocytic And Granulocytic HL-60/S4 Cells" (2019). Pharmaceutical Sciences Faculty Publications. 16.
https://dune.une.edu/pharmsci_facpubs/16
Supplementary materials .zip file
Comments
Originally published:
Elsie C. Jacobson, Lekha Jain, Mark H. Vickers, Ada L. Olins, Donald E. Olins, Jo K. Perry, Justin M. O’Sullivan (2019), TNF-α Differentially Regulates Cell Cycle Genes in Promyelocytic and Granulocytic HL-60/S4 Cells. G3: GENES, GENOMES, GENETICS August 1, 2019 vol. 9 no. 8 2775-2786;https://doi.org/10.1534/g3.119.400361
Copyright © 2019 Jacobson et al.This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Supplementary file retrieved from:
Jacobson, Elsie C.; Jain, Lekha; Vickers, Mark H.; Olins, Ada L.; Olins, Donald E.; Perry, Jo K.; et al. (2019): Supplemental Material for Jacobsen et al., 2019. GSA Journals. Dataset. https://doi.org/10.25387/g3.8146097.v1
Supplemental materials descriptions:
Supplementary tables 1-22. 1. Significantly differentially expressed genes in promyelocytes treated with TNF-a, differentiated into granulocytes and macrophages, and granulocytes treated with TNF-a. 2. RT-qPCR and RNA-seq of CDK1, TNF, and VCAM1. 3-21. Functional analysis summary tables of GSEA, GO, KEGG, and hallmark terms enriched in subsets of differentially expressed genes. 22. Primers and probes used for RT-qPCR validation.
Supplementary figure 1. PCA of VST-normalized transcript counts show conditions cluster together in A) promyelocytes treated with TNF-a, B) granulocytes treated with TNF-a, and C) promyelocytes differentiated into granulocytes and macrophages.