TY - JOUR
T1 - Comparison of the PU.1 transcriptional regulome and interactome in human and mouse inflammatory dendritic cells
AU - Scheenstra, Maaike R.
AU - Martínez-Botía, Patricia
AU - Acebes-Huerta, Andrea
AU - Brouwer, Rutger W. W.
AU - Caballero-Sánchez, Noemí
AU - Gillemans, Nynke
AU - de Bleser, Pieter
AU - Nota, Benjamin
AU - de Cuyper, Iris M.
AU - Salunkhe, Vishal
AU - Woltman, Andrea M.
AU - van de Laar, Lianne
AU - Rijkers, Erikjan
AU - Demmers, Jeroen A. A.
AU - van IJcken, Wilfred F. J.
AU - Philipsen, Sjaak
AU - van den Berg, Timo K.
AU - Kuijpers, Taco W.
AU - Gutiérrez, Laura
N1 - Funding Information:
This work was supported by a VENI grant from the Dutch Research Council (NWO; VENI 863.09.012) and a RYC fellowship from the Spanish Ministerio de Economía y Competitividad (RYC‐2013‐12587) to LG, a Severo Ochoa Grant (PA‐20‐PF‐BP19‐014) from the Consejería de Ciencia, Innovación y Universidad del Principado de Asturias (Spain) to PMB and a postdoctoral 2018 intramural grant (Fundación para la Investigación y la Innovación Biosanitaria de Asturias ‐FINBA‐, Spain) to AAH. We thank Jeremy Carver (UCSD) for assistance with proteomics data upload to MassIVE repository.
Funding Information:
This work was supported by a VENI grant from the Dutch Research Council (NWO; VENI 863.09.012) and a RYC fellowship from the Spanish Ministerio de Econom?a y Competitividad (RYC-2013-12587) to LG, a Severo Ochoa Grant (PA-20-PF-BP19-014) from the Consejer?a de Ciencia, Innovaci?n y Universidad del Principado de Asturias (Spain) to PMB and a postdoctoral 2018 intramural grant (Fundaci?n para la Investigaci?n y la Innovaci?n Biosanitaria de Asturias -FINBA-, Spain) to AAH. We thank Jeremy Carver (UCSD) for assistance with proteomics data upload to MassIVE repository.
Publisher Copyright:
©2020 Society for Leukocyte Biology
PY - 2021/10
Y1 - 2021/10
N2 - Dendritic cells (DCs) are key immune modulators and are able to mount immune responses or tolerance. DC differentiation and activation imply a plethora of molecular and cellular responses, including transcriptional changes. PU.1 is a highly expressed transcription factor in DCs and coordinates relevant aspects of DC biology. Due to their role as immune regulators, DCs pose as a promising immunotherapy tool. However, some of their functional features, such as survival, activation, or migration, are compromised due to the limitations to simulate in vitro the physiologic DC differentiation process. A better knowledge of transcriptional programs would allow the identification of potential targets for manipulation with the aim of obtaining “qualified” DCs for immunotherapy purposes. Most of the current knowledge regarding DC biology derives from studies using mouse models, which not always find a parallel in human. In the present study, we dissect the PU.1 transcriptional regulome and interactome in mouse and human DCs, in the steady state or LPS activated. The PU.1 transcriptional regulome was identified by performing PU.1 chromatin immunoprecipitation followed by high-throughput sequencing and pairing these data with RNAsequencing data. The PU.1 interactome was identified by performing PU.1 immunoprecipitation followed by mass spectrometry analysis. Our results portray PU.1 as a pivotal factor that plays an important role in the regulation of genes required for proper DC activation and function, and assures the repression of nonlineage genes. The interspecies differences between human and mouse DCs are surprisingly substantial, highlighting the need to study the biology of human DCs.
AB - Dendritic cells (DCs) are key immune modulators and are able to mount immune responses or tolerance. DC differentiation and activation imply a plethora of molecular and cellular responses, including transcriptional changes. PU.1 is a highly expressed transcription factor in DCs and coordinates relevant aspects of DC biology. Due to their role as immune regulators, DCs pose as a promising immunotherapy tool. However, some of their functional features, such as survival, activation, or migration, are compromised due to the limitations to simulate in vitro the physiologic DC differentiation process. A better knowledge of transcriptional programs would allow the identification of potential targets for manipulation with the aim of obtaining “qualified” DCs for immunotherapy purposes. Most of the current knowledge regarding DC biology derives from studies using mouse models, which not always find a parallel in human. In the present study, we dissect the PU.1 transcriptional regulome and interactome in mouse and human DCs, in the steady state or LPS activated. The PU.1 transcriptional regulome was identified by performing PU.1 chromatin immunoprecipitation followed by high-throughput sequencing and pairing these data with RNAsequencing data. The PU.1 interactome was identified by performing PU.1 immunoprecipitation followed by mass spectrometry analysis. Our results portray PU.1 as a pivotal factor that plays an important role in the regulation of genes required for proper DC activation and function, and assures the repression of nonlineage genes. The interspecies differences between human and mouse DCs are surprisingly substantial, highlighting the need to study the biology of human DCs.
KW - PU.1
KW - dendritic cells
KW - interactome
KW - interspecies
KW - transcription factor
KW - transcriptome
UR - https://www.scopus.com/pages/publications/85096992919
U2 - 10.1002/JLB.6A1219-711RRR
DO - 10.1002/JLB.6A1219-711RRR
M3 - Article
C2 - 33289106
SN - 0741-5400
VL - 110
SP - 735
EP - 751
JO - Journal of leukocyte biology
JF - Journal of leukocyte biology
IS - 4
ER -