Decoding environmentally driven gene regulatory networks in hepatic macrophages

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Mashito Sakai from the University of California, San Diego.

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Date: Tuesday, December 10, 2019

Time: 11:00-12:00

Venue: D015, Level D, Lab 1

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Speaker:

Dr. Mashito Sakai, Postdoctoral Scholar, University of California, San Diego

Title:
Decoding environmentally driven gene regulatory networks in hepatic macrophages

Abstract:

   Tissue environment has an instructive role in establishing resident macrophage phenotypes. Here, we characterize transcriptomic and epigenetic changes in repopulating liver macrophages, following acute Kupffer cell (liver resident macrophage) depletion, as a means to infer signaling pathways and transcription factors that promote Kupffer cell differentiation. We obtain evidence for a two-step model in which liver-derived signals that include DLL4, TGF-β, and desmosterol induce Kupffer cell differentiation by regulating the expression and activities of RBPJ, SMADs, and LXRα (Sakai M, Troutman TD, Seidman JS et al. 2019, Immunity).

   Tissue-resident macrophages and recruited monocyte-derived macrophages contribute to host defense but also play pathological roles in a diverse range of human diseases. Next, we use a combination of genetic, genomic, and imaging approaches to investigate the origins and epigenetic trajectories of hepatic myeloid cells during a diet-induced model of non-alcoholic steatohepatitis (NASH). We provide evidence that distinct micro-environments within the NASH liver induce strikingly divergent transcriptomes of resident and infiltrating cells. Myeloid cell diversification results from both remodeling open chromatin landscapes of recruited monocytes and altering activities of pre-existing enhancers of resident Kupffer cells.

   Collectively, these findings provide 1) a framework for understanding how a common macrophage progenitor cell acquires tissue-specific phenotypes and 2) evidence that niche-specific combinations of disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct programs of gene expression and corresponding phenotypes.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit