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The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

Charlotte Scott (UGent) , Bieke Soen (UGent) , Liesbet Martens (UGent) , Nicolas Skrypek (UGent) , Wouter Saelens (UGent) , Joachim Taminau (UGent) , Gillian Blancke (UGent) , Gert Van Isterdael (UGent) , Danny Huylebroeck, Jody Haigh (UGent) , et al.
(2016) JOURNAL OF EXPERIMENTAL MEDICINE. 213(6). p.897-911
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Abstract
Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.
Keywords
FACTOR-BINDING SITES, TERMINAL DIFFERENTIATION, INTESTINAL LAMINA PROPRIA, DENDRITIC CELL-DEVELOPMENT, CLONOGENIC PROGENITOR, SUBSET DEVELOPMENT, SIGNALING CONTROLS, BONE-MARROW, FACTOR E2-2, IN-VIVO

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Chicago
Scott, Charlotte, Bieke Soen, Liesbet Martens, Nicolas Skrypek, Wouter Saelens, Joachim Taminau, Gillian Blancke, et al. 2016. “The Transcription Factor Zeb2 Regulates Development of Conventional and Plasmacytoid DCs by Repressing Id2.” Journal of Experimental Medicine 213 (6): 897–911.
APA
Scott, C., Soen, B., Martens, L., Skrypek, N., Saelens, W., Taminau, J., Blancke, G., et al. (2016). The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. JOURNAL OF EXPERIMENTAL MEDICINE, 213(6), 897–911.
Vancouver
1.
Scott C, Soen B, Martens L, Skrypek N, Saelens W, Taminau J, et al. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. JOURNAL OF EXPERIMENTAL MEDICINE. 2016;213(6):897–911.
MLA
Scott, Charlotte, Bieke Soen, Liesbet Martens, et al. “The Transcription Factor Zeb2 Regulates Development of Conventional and Plasmacytoid DCs by Repressing Id2.” JOURNAL OF EXPERIMENTAL MEDICINE 213.6 (2016): 897–911. Print.
@article{8055512,
  abstract     = {Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.},
  author       = {Scott, Charlotte and Soen, Bieke and Martens, Liesbet and Skrypek, Nicolas and Saelens, Wouter and Taminau, Joachim and Blancke, Gillian and Van Isterdael, Gert and Huylebroeck, Danny and Haigh, Jody and Saeys, Yvan and Guilliams, Martin and Lambrecht, Bart and Berx, Geert},
  issn         = {0022-1007},
  journal      = {JOURNAL OF EXPERIMENTAL MEDICINE},
  language     = {eng},
  number       = {6},
  pages        = {897--911},
  title        = {The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2},
  url          = {http://dx.doi.org/10.1084/jem.20151715},
  volume       = {213},
  year         = {2016},
}

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