Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

Soucié, Erinn; Weng, Ziming; Geirsdóttir, Laufey; Molawi, Kaaweh; Maurizio, Julien; Fenouil, Romain; Mossadegh-Keller, Noushine; Gimenez, Grégory; Vanhille, Laurent; Beniazza, Meryam; Favret, Jérémy; Berruyer-Pouyet, Carole; Perrin, Pierre; Hacohen, Nir; Andrau, Jean-Christophe; Ferrier, Pierre; Dubreuil, Patrice; Sidow, Arend; Sieweke, Michael H.

doi:10.1126/science.aad5510

Cited by 212 publications

(230 citation statements)

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“…ZBTB16 is also involved in type 2 innate lymphoid cell function (63), NKT cell differentiation (64), and regulation of inflammatory signaling (65). MAFB is associated with macrophage differentiation (36,66). FER plays a role in leukocyte recruitment and intestinal barrier function in response to bacterial lipopolysaccharide recognition (67).…”

Section: I N I C a L M E D I C I N Ementioning

confidence: 99%

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn’s disease patients

Liu¹,

Naito²,

Liu³

et al. 2017

JCI Insight

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IntroductionCrohn's disease (CD) and ulcerative colitis are 2 main classical types of inflammatory bowel disease (IBD) (1, 2). The etiology of IBD involves genetic susceptibility and environmental triggers. Over 200 single nucleotide polymorphisms (SNPs) have been associated with susceptibility to IBD (3-7). This complex genetic network indicates that IBD likely encompasses more than the 2 classical subtypes. Therefore, novel, rationally designed biomarkers that can lead to disease stratification and personalized treatments are needed (8). One candidate method to subtype CD is to define the morphological patterns of small intestinal Paneth cells based on the intracellular distribution of granules containing antimicrobial proteins (Paneth cell phenotypes) (7). Paneth cells are specialized secretory cells located at the bases of the crypts of Lieberkühn in the small intestine (9-11). These cells produce a wide repertoire of antimicrobial BACKGROUND. Morphological patterns of Paneth cells are a prognostic biomarker in Western Crohn's disease (CD) patients, and are associated with autophagy-associated ATG16L1 and NOD2 variants. We hypothesized that genetic determinants of Paneth cell phenotype in other ethnic CD cohorts are distinct but also involved in autophagy.

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Section: I N I C a L M E D I C I N Ementioning

confidence: 99%

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn’s disease patients

Liu¹,

Naito²,

Liu³

et al. 2017

JCI Insight

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“…The main autophagic processes are unaf-fected, whereas mitophagy which would have been useful to eliminate the dysfunctionnal mitochondria is totally abolished. Our results are discussed in light of the recent results, especially, the elegant work of Wang's team 3 , that bridges the gap between abnormal ROS production in BTHS derived-iPSCs and the mechanical defect of the sarcomeric structure and function. (286), RIMLS, Radboudumc, Nijmegen, The Netherlands ATP can be produced in the cytosol by glycolytic conversion of glucose (GLC) into pyruvate (PYR).…”

mentioning

confidence: 77%

“…Mt DNA content was assessed by real time qPCR as the Mt/N ratio, mitochondrial function was assessed by measuring RNAs involved in mitochondrial life cycle and by examining the mitochondrial morphology of the cells, and metabolic function was assessed extra-flux analysis using the seahorse system. Results: Hyperglycemia triggered an early increase in MtDNA content in cultured renal cells, which was not accompanied by increased mitochondrial transcription/translation, instead the cells showed altered mitochondrial morphology, increased MYD88/ NF-jB, and displayed reduced mitochondrial bioenergetics, with significantly reduced maximal respiration and reserve capacity (3). In human subjects, diabetes led to increased circulating MtDNA, however a reduction in MtDNA was observed in patients who developed nephropathy or retinopathy, in parallel with increased MtDNA damage and inflammation (4).…”

mentioning

confidence: 99%

“…Ex vivo characterization of calcium pyrophosphate-based osteoarticular calcifications by X-ray diffraction and Raman spectroscopy Although several techniques have been used for the characterization of ex vivo calcium pyrophosphate (CPP: Ca 2 P 2 O 7 ÁnH 2 O) deposits associated to osteoarthritis, [1][2][3][4] little is known from a chemical point of view on these phases which are difficult to synthesize, could evolve during their formation in vivo and be altered after extraction during conservation, preparation and analysis. Recently, Gras et al established a protocol allowing a one-step and fast synthesis of four phases of CPP of biological interest by monitoring the pH and temperature during the synthesis.…”

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confidence: 99%

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Workshops

2016

Eur J Clin Investigation

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Background: Macular edema, a frequently encountered complication of diabetic retinopathy (DR), results from alterations of the blood retinal barrier (BRB) and leads to modifications of the retinal pigmented epithelium (RPE) functions. Osmolar changes of the surrounding medium could be responsible for modifications of the RPE functions leading to disturbance of retinal homeostasis. The expression, activation and function of the key hyperosmolar response factor Tonicity Enhancer Binding Protein (TonEBP also called nuclear factor of activated T-cell 5 -NFTA5) was investigated in ARPE-19 cells, derived from human RPE, in response to hyperosmolar stimulation. Material and methods: ARPE-19 cells were exposed to hyperosmolar medium. TonEBP mRNA and protein levels were quantified by qRT-PCR and semi-quantitative Western blot. TonEBP nuclear translocation was investigated by immunofluorescence. TonEBP transactivation activity was measured using a reported plasmid containing TonEBP binding sites. Results: Hyperosmolar stimulation of ARPE-19 cells induced a dose-dependent increase in TonEBP mRNA and protein levels, as well as TonEBP nuclear translocation. TonEBP transactivation activity was demonstrated using a reporter plasmid containing TonEBP binding sites. A dominant negative form of TonEBP abolished NaCl-induced increase in TonEBP transactivation activity, and inhibited the increase of the target genes aldose reductase and sodium-dependent taurine transporter mRNA levels. SB203580, an inhibitor of two of p38 protein kinase inhibited the TonEBP nuclear translocation and transactivation activity in ARPE-19 cells exposed to hyperosmolar stimulation. Conclusions: Our data demonstrate the involvement of TonEBP in the mechanisms responsible for osmoadaptation to hyperosmolar stress in RPE cells. These data open new perspectives for the analysis of the mechanisms involved in the modification of functions of the RPE during macular edema. 1.02Treatment of symptomatic familial mediterranean fever (FMF). Colchicine, biologic agents and more. experience in apulia and basilicata regions, Italy † Gastrointestinal Endoscopy Unit, Ospedale della Murgia "F. Perinei", Altamura, Bari, Italy Background: FMF is rare autosomal recessive autoinflammatory disorder involving the innate immunity and affecting almost exclusively populations with Mediterranean origin. FMF cases are spread across Europe because of the historical migrations. A cluster of Italian patients was recently identified in Apulia and Basilicata (Altamura, Matera). Clinical features include recurrent episodes of fever, leukocitosis, serositis (peritonitis or pleuritis, arthritis), myalgia or erysipelas-like skin lesions, lasting 12-72 hrs. The MEFV gene mutations on chromosome 16p13.3 encodes the abnormal pyrin (marenostrin), a protein expressed in granulocytes, monocytes, serosal and synovial fibroblasts and involved in the activation of caspase-1 and the processing and release of active pro-inflammatory IL-1b. Methods: Since 1972, maintenance therapy with colchicine, a tr...

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“…Even after differentiation, they can selfrenew in a process mediated by the down-regulation of the TFs MafB and cMaf and the rewiring of the embryonic stem cell self-renewal network [22 ]. During mouse embryogenesis, the core macrophage program driven by PU.1 is rapidly diversified by the action of lineage-determining TFs (LDTFs), which integrate specific cues from the microenvironment to orchestrate the deposition of active histone modification marks ( Figure 1) [6 ,7 ,23-26].…”

Section: The Temporal and Spatial Properties Of Macrophage Regulatorymentioning

confidence: 99%

Gene regulatory mechanisms underlying the intestinal innate immune response

Meireles-Filho

Deplancke

2017

Current Opinion in Genetics & Development

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In the mammalian gastrointestinal tract, distinct types of cells, including epithelial cells and macrophages, collaborate to eliminate ingested pathogens while striving to preserve the commensal microbiota. The underlying innate immune response is driven by significant gene expression changes in each cell, and recent work has provided novel insights into the gene regulatory mechanisms that mediate such transcriptional changes. These mechanisms differ from those underlying the canonical cellular differentiation model in which a sequential deposition of DNA methylation and histone modification marks progressively restricts the chromatin landscape. Instead, inflammatory macrophages and intestinal epithelial cells appear to largely rely on transcription factors that explore an accessible chromatin landscape to generate dynamic stimulus-specific and spatial-specific physiological responses.

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Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

Cited by 212 publications

References 40 publications

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn’s disease patients

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn’s disease patients

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Gene regulatory mechanisms underlying the intestinal innate immune response

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