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.
Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment
Abbreviations used in this paper: bZIP, basic region-leucine zipper; C/EBP, CCAAT/enhancer binding protein; DC, dendritic cells; EGFP, enhanced green fluorescent protein; Eo, eosinophil; EPO, eosinophil peroxidase; FBS, fetal bovine serum; IRES, internal ribosome entry site; LC, Langerhans cells; MSCV, murine stem cell virus; NGFR, nerve growth factor receptor; RT, reverse transcription; SCF, stem cell factor.
Atsushi Iwama, Mitsujiro Osawa, Ryutaro Hirasawa, Noriko Uchiyama, Shin Kaneko, Masafumi Onodera, Kazuko Shibuya, Akira Shibuya, Charles Vinson, Daniel G. Tenen, Hiromitsu Nakauchi; Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment . J Exp Med 4 March 2002; 195 (5): 547–558. doi: https://doi.org/10.1084/jem.20011465
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