NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells
Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Ana...
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doaj-cd04ad37166f4a689ad18d1848c8497c2021-06-01T01:44:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01225902590210.3390/ijms22115902NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic CellsStefan Nagel0Claudia Pommerenke1Corinna Meyer2Hans G. Drexler3Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ—German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, GermanyDepartment of Human and Animal Cell Lines, Leibniz-Institute DSMZ—German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, GermanyDepartment of Human and Animal Cell Lines, Leibniz-Institute DSMZ—German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, GermanyDepartment of Human and Animal Cell Lines, Leibniz-Institute DSMZ—German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, GermanyRecently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.https://www.mdpi.com/1422-0067/22/11/5902AMLcell lineshomeoboxNKL-codeT-ALL |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stefan Nagel Claudia Pommerenke Corinna Meyer Hans G. Drexler |
spellingShingle |
Stefan Nagel Claudia Pommerenke Corinna Meyer Hans G. Drexler NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells International Journal of Molecular Sciences AML cell lines homeobox NKL-code T-ALL |
author_facet |
Stefan Nagel Claudia Pommerenke Corinna Meyer Hans G. Drexler |
author_sort |
Stefan Nagel |
title |
NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells |
title_short |
NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells |
title_full |
NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells |
title_fullStr |
NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells |
title_full_unstemmed |
NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells |
title_sort |
nkl homeobox gene ventx is part of a regulatory network in human conventional dendritic cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-05-01 |
description |
Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function. |
topic |
AML cell lines homeobox NKL-code T-ALL |
url |
https://www.mdpi.com/1422-0067/22/11/5902 |
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