Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

Xiaodi Wu; Carlos G. Briseño; Gary E. Grajales-Reyes; Malay Haldar; Arifumi Iwata; Nicole M. Kretzer; K. C. Wumesh; Roxane Tussiwand; Yujiro Higashi; Theresa L. Murphy; Kenneth M. Murphy

doi:10.1073/pnas.1611408114

Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

Xiaodi Wu, Carlos G. Briseño, Gary E. Grajales-Reyes, Malay Haldar, Arifumi Iwata, Nicole M. Kretzer, K. C. Wumesh, Roxane Tussiwand, Yujiro Higashi, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6C^hi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.

Original language	English
Pages (from-to)	14775-14780
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	51
DOIs	https://doi.org/10.1073/pnas.1611408114
State	Published - Dec 20 2016

Keywords

Monocyte
Plasmacytoid dendritic cell
Transcription factor

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10.1073/pnas.1611408114

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Wu, X., Briseño, C. G., Grajales-Reyes, G. E., Haldar, M., Iwata, A., Kretzer, N. M., Wumesh, K. C., Tussiwand, R., Higashi, Y., Murphy, T. L., & Murphy, K. M. (2016). Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate. Proceedings of the National Academy of Sciences of the United States of America, 113(51), 14775-14780. https://doi.org/10.1073/pnas.1611408114

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title = "Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate",

abstract = "Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.",

keywords = "Monocyte, Plasmacytoid dendritic cell, Transcription factor",

author = "Xiaodi Wu and Brise{\~n}o, {Carlos G.} and Grajales-Reyes, {Gary E.} and Malay Haldar and Arifumi Iwata and Kretzer, {Nicole M.} and Wumesh, {K. C.} and Roxane Tussiwand and Yujiro Higashi and Murphy, {Theresa L.} and Murphy, {Kenneth M.}",

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doi = "10.1073/pnas.1611408114",

language = "English",

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Wu, X, Briseño, CG, Grajales-Reyes, GE, Haldar, M, Iwata, A, Kretzer, NM, Wumesh, KC, Tussiwand, R, Higashi, Y, Murphy, TL & Murphy, KM 2016, 'Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 51, pp. 14775-14780. https://doi.org/10.1073/pnas.1611408114

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T1 - Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

AU - Wu, Xiaodi

AU - Briseño, Carlos G.

AU - Grajales-Reyes, Gary E.

AU - Haldar, Malay

AU - Iwata, Arifumi

AU - Kretzer, Nicole M.

AU - Wumesh, K. C.

AU - Tussiwand, Roxane

AU - Higashi, Yujiro

AU - Murphy, Theresa L.

AU - Murphy, Kenneth M.

PY - 2016/12/20

Y1 - 2016/12/20

N2 - Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.

AB - Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.

KW - Monocyte

KW - Plasmacytoid dendritic cell

KW - Transcription factor

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Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

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