Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity

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Item Type:	Article
Title:	Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity
Creators Name:	Rauschmeier, R., Gustafsson, C., Reinhardt, A., A-Gonzalez, N., Tortola, L., Cansever, D., Subramanian, S., Taneja, R., Rossner, M.J., Sieweke, M.H., Greter, M., Månsson, R., Busslinger, M. and Kreslavsky, T.
Abstract:	Tissues in multicellular organisms are populated by resident macrophages, which perform both generic and tissue-specific functions. The latter are induced by signals from the microenvironment and rely on unique tissue-specific molecular programs requiring the combinatorial action of tissue-specific and broadly expressed transcriptional regulators. Here, we identify the transcription factors Bhlhe40 and Bhlhe41 as novel regulators of alveolar macrophages (AMs)-a population that provides the first line of immune defense and executes homeostatic functions in lung alveoli. In the absence of these factors, AMs exhibited decreased proliferation that resulted in a severe disadvantage of knockout AMs in a competitive setting. Gene expression analyses revealed a broad cell-intrinsic footprint of Bhlhe40/Bhlhe41 deficiency manifested by a downregulation of AM signature genes and induction of signature genes of other macrophage lineages. Genome-wide characterization of Bhlhe40 DNA binding suggested that these transcription factors directly repress the expression of lineage-inappropriate genes in AMs. Taken together, these results identify Bhlhe40 and Bhlhe41 as key regulators of AM self-renewal and guardians of their identity.
Keywords:	Alveolar Macrophages, Bhlhe40, Bhlhe41, Self-Renewal, Tissue-Resident Macrophages, Animals, Mice
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	EMBO Press / Wiley
Volume:	38
Number:	19
Page Range:	e101233
Date:	1 October 2019
Official Publication:	https://doi.org/10.15252/embj.2018101233
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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