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Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment

Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characte...

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Autores principales: Iwama, Atsushi, Osawa, Mitsujiro, Hirasawa, Ryutaro, Uchiyama, Noriko, Kaneko, Shin, Onodera, Masafumi, Shibuya, Kazuko, Shibuya, Akira, Vinson, Charles, Tenen, Daniel G., Nakauchi, Hiromitsu
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193769/
https://www.ncbi.nlm.nih.gov/pubmed/11877478
http://dx.doi.org/10.1084/jem.20011465
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author Iwama, Atsushi
Osawa, Mitsujiro
Hirasawa, Ryutaro
Uchiyama, Noriko
Kaneko, Shin
Onodera, Masafumi
Shibuya, Kazuko
Shibuya, Akira
Vinson, Charles
Tenen, Daniel G.
Nakauchi, Hiromitsu
author_facet Iwama, Atsushi
Osawa, Mitsujiro
Hirasawa, Ryutaro
Uchiyama, Noriko
Kaneko, Shin
Onodera, Masafumi
Shibuya, Kazuko
Shibuya, Akira
Vinson, Charles
Tenen, Daniel G.
Nakauchi, Hiromitsu
author_sort Iwama, Atsushi
collection PubMed
description Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characterized as key regulators for the development and function of the myeloid system. However, the roles of C/EBP transcription factors have not been fully identified because of functional redundancy among family members. Using high titer–retroviral infection, we demonstrate that a dominant-negative C/EBP completely blocked the granulocyte–macrophage commitment of human myeloid progenitors. Alternatively, Langerhans cell (LC) commitment was markedly facilitated in the absence of tumor necrosis factor (TNF)α, a strong inducer of LC development, whereas expression of wild-type C/EBP in myeloid progenitors promoted granulocytic differentiation, and completely inhibited TNFα-dependent LC development. On the other hand, expression of wild-type PU.1 in myeloid progenitors triggered LC development in the absence of TNFα, and its instructive effect was canceled by coexpressed C/EBP. Our findings establish reciprocal roles for C/EBP and PU.1 in LC development, and provide new insight into the molecular mechanism of LC development, which has not yet been well characterized.
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spelling pubmed-21937692008-04-14 Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment Iwama, Atsushi Osawa, Mitsujiro Hirasawa, Ryutaro Uchiyama, Noriko Kaneko, Shin Onodera, Masafumi Shibuya, Kazuko Shibuya, Akira Vinson, Charles Tenen, Daniel G. Nakauchi, Hiromitsu J Exp Med Original Article Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characterized as key regulators for the development and function of the myeloid system. However, the roles of C/EBP transcription factors have not been fully identified because of functional redundancy among family members. Using high titer–retroviral infection, we demonstrate that a dominant-negative C/EBP completely blocked the granulocyte–macrophage commitment of human myeloid progenitors. Alternatively, Langerhans cell (LC) commitment was markedly facilitated in the absence of tumor necrosis factor (TNF)α, a strong inducer of LC development, whereas expression of wild-type C/EBP in myeloid progenitors promoted granulocytic differentiation, and completely inhibited TNFα-dependent LC development. On the other hand, expression of wild-type PU.1 in myeloid progenitors triggered LC development in the absence of TNFα, and its instructive effect was canceled by coexpressed C/EBP. Our findings establish reciprocal roles for C/EBP and PU.1 in LC development, and provide new insight into the molecular mechanism of LC development, which has not yet been well characterized. The Rockefeller University Press 2002-03-04 /pmc/articles/PMC2193769/ /pubmed/11877478 http://dx.doi.org/10.1084/jem.20011465 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Iwama, Atsushi
Osawa, Mitsujiro
Hirasawa, Ryutaro
Uchiyama, Noriko
Kaneko, Shin
Onodera, Masafumi
Shibuya, Kazuko
Shibuya, Akira
Vinson, Charles
Tenen, Daniel G.
Nakauchi, Hiromitsu
Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
title Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
title_full Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
title_fullStr Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
title_full_unstemmed Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
title_short Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
title_sort reciprocal roles for ccaat/enhancer binding protein (c/ebp) and pu.1 transcription factors in langerhans cell commitment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193769/
https://www.ncbi.nlm.nih.gov/pubmed/11877478
http://dx.doi.org/10.1084/jem.20011465
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