scholarly journals Maximal Induction of a Subset of Interferon Target Genes Requires the Chromatin-Remodeling Activity of the BAF Complex

2002 ◽  
Vol 22 (18) ◽  
pp. 6471-6479 ◽  
Author(s):  
Hong Liu ◽  
Hyeog Kang ◽  
Rui Liu ◽  
Xin Chen ◽  
Keji Zhao
Keyword(s):  
Chromatin Remodeling ◽  
Target Genes ◽  
Transcription Activator ◽  
Baf Complex ◽  
Antiproliferative Effects ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Maximal Induction ◽  
Antiproliferative Activities

ABSTRACT The mammalian SWI/SNF-like chromatin-remodeling BAF complex plays several important roles in controlling cell proliferation and differentiation. Interferons (IFNs) are key mediators of cellular antiviral and antiproliferative activities. In this report, we demonstrate that the BAF complex is required for the maximal induction of a subset of IFN target genes by alpha IFN (IFN-α). The BAF complex is constitutively associated with the IFITM3 promoter in vivo and facilitates the chromatin remodeling of the promoter upon IFN-α induction. Furthermore, we show that the ubiquitous transcription activator Sp1 interacts with the BAF complex in vivo and augments the BAF-mediated activation of the IFITM3 promoter. Sp1 binds constitutively to the IFITM3 promoter in the absence of the BAF complex, suggesting that it may recruit and/or stabilize the BAF complex binding to the IFITM3 promoter. Our results bring new mechanistic insights into the antiproliferative effects of the chromatin-remodeling BAF complex.

MicroRNA Determines the Fate of Intestinal Epithelial Cell Differentiation and Regulates Intestinal Diseases

2019 ◽  
Vol 20 (7) ◽  
pp. 666-673 ◽  
Author(s):  
Sujuan Ding ◽  
Gang Liu ◽  
Hongmei Jiang ◽  
Jun Fang
Keyword(s):  
Target Genes ◽  
Gastrointestinal Disease ◽  
Intestinal Barrier ◽  
Vital Role ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Intestinal Function ◽  
Cell Fates ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The rapid self-renewal of intestinal epithelial cells enhances intestinal function, promotes the nutritional needs of animals and strengthens intestinal barrier function to resist the invasion of foreign pathogens. MicroRNAs (miRNAs) are a class of short-chain, non-coding RNAs that regulate stem cell proliferation and differentiation by down-regulating hundreds of conserved target genes after transcription via seed pairing to the 3' untranslated regions. Numerous studies have shown that miRNAs can improve intestinal function by participating in the proliferation and differentiation of different cell populations in the intestine. In addition, miRNAs also contribute to disease regulation and therefore not only play a vital role in the gastrointestinal disease management but also act as blood or tissue biomarkers of disease. As changes to the levels of miRNAs can change cell fates, miRNA-mediated gene regulation can be used to update therapeutic strategies and approaches to disease treatment.

scholarly journals Mechanics of the cellular microenvironment as perceived by cells in vivo

2021 ◽  
Author(s):  
Alessandro Mongera ◽  
Marie Pochitaloff ◽  
Hannah J. Gustafson ◽  
Georgina A. Stooke-Vaughan ◽  
Payam Rowghanian ◽  
...  
Keyword(s):  
Stress Relaxation ◽  
Mechanical Parameters ◽  
Cellular Microenvironment ◽  
Stem Cell Maintenance ◽  
Quantitative Studies ◽  
Cell Proliferation And Differentiation ◽  
3D Microenvironment ◽  
Proliferation And Differentiation

Tissue morphogenesis and repair, as well as organ homeostasis, require cells to constantly monitor their 3D microenvironment and adapt their behaviors in response to local biochemical and mechanical cues1-6. In vitro studies have shown that substrate stiffness and stress relaxation are important mechanical parameters in the control of cell proliferation and differentiation, stem cell maintenance, cell migration 7-11, as well as tumor progression and metastasis12,13. Yet, the mechanical parameters of the microenvironment that cells perceive in vivo, within 3D tissues, remain unknown. In complex materials with strain- and time-dependent material properties, the perceived mechanical parameters depend both on the strain and timescales at which the material is mechanically probed14. Here, we quantify in vivo and in situ the mechanics of the cellular microenvironment that cells probe during vertebrate presomitic mesoderm (PSM) specification. By analyzing the magnitude and dynamics of endogenous, cell-generated strains, we show that individual cells preferentially probe the stiffness associated with deformations of the supracellular, foam-like tissue architecture. We reveal how stress relaxation leads to a perceived microenvironment stiffness that decreases over time, with cells probing the softest regime. While stress relaxation timescales are spatially uniform in the tissue, most mechanical parameters, including those probed by cells, vary along the anteroposterior axis, as mesodermal progenitors commit to different lineages. Understanding the mechanical parameters that cells probe in their native 3D environment is important for quantitative studies of mechanosensation in vivo2-4,6,15 and can help design scaffolds for tissue engineering applications16-18.

Hedgehog signals regulate multiple aspects of gastrointestinal development

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2763-2772 ◽  
Author(s):  
M. Ramalho-Santos ◽  
D.A. Melton ◽  
A.P. McMahon
Keyword(s):  
Gastrointestinal Tract ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Critical Role ◽  
Indian Hedgehog ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mesodermal Origin ◽  
Gut Endoderm

The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.

scholarly journals Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity

2018 ◽  
Vol 115 (26) ◽  
pp. 6786-6791 ◽  
Author(s):  
Jiaxi Wu ◽  
Huaizhu Wu ◽  
Jinping An ◽  
Christie M. Ballantyne ◽  
Jason G. Cyster
Keyword(s):  
Critical Role ◽  
T Cell Proliferation ◽  
Cell Capture ◽  
Antigen Uptake ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Missing Self

CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). CD11c can bind complement iC3b and mediate phagocytosis in vitro, for which it is also referred to as complement receptor 4. However, the functions of this prominent marker protein in DCs, especially in vivo, remain poorly defined. Here, in the process of studying DC activation and immune responses induced by cells lacking self-CD47, we found that DC capture of CD47-deficient cells and DC activation was dependent on the integrin-signaling adaptor Talin1. Specifically, CD11c and its partner Itgb2 were required for DC capture of CD47-deficient cells. CD11b was not necessary for this process but could partially compensate in the absence of CD11c. Mice with DCs lacking Talin1, Itgb2, or CD11c were defective in supporting T-cell proliferation and differentiation induced by CD47-deficient cell associated antigen. These findings establish a critical role for CD11c in DC antigen uptake and activation in vivo. They may also contribute to understanding the functional mechanism of CD47-blockade therapies.

scholarly journals Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shinichiro Hayashi ◽  
Ichiro Manabe ◽  
Yumi Suzuki ◽  
Frédéric Relaix ◽  
Yumiko Oishi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Biological Processes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Acting In Concert

Krüppel-like factor 5 (Klf5) is a zinc-finger transcription factor that controls various biological processes, including cell proliferation and differentiation. We show that Klf5 is also an essential mediator of skeletal muscle regeneration and myogenic differentiation. During muscle regeneration after injury (cardiotoxin injection), Klf5 was induced in the nuclei of differentiating myoblasts and newly formed myofibers expressing myogenin in vivo. Satellite cell-specific Klf5 deletion severely impaired muscle regeneration, and myotube formation was suppressed in Klf5-deleted cultured C2C12 myoblasts and satellite cells. Klf5 knockdown suppressed induction of muscle differentiation-related genes, including myogenin. Klf5 ChIP-seq revealed that Klf5 binding overlaps that of MyoD and Mef2, and Klf5 physically associates with both MyoD and Mef2. In addition, MyoD recruitment was greatly reduced in the absence of Klf5. These results indicate that Klf5 is an essential regulator of skeletal muscle differentiation, acting in concert with myogenic transcription factors such as MyoD and Mef2.

scholarly journals A role for GPx3 in activity of normal and leukemia stem cells

2012 ◽  
Vol 209 (5) ◽  
pp. 895-901 ◽  
Author(s):  
Olivier Herault ◽  
Kristin J. Hope ◽  
Eric Deneault ◽  
Nadine Mayotte ◽  
Jalila Chagraoui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Low Frequency ◽  
Leukemia Stem Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation ◽  
Novel Target

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs.

scholarly journals Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation

2005 ◽  
Vol 168 (7) ◽  
pp. 1065-1076 ◽  
Author(s):  
Alka Mansukhani ◽  
Davide Ambrosetti ◽  
Greg Holmes ◽  
Lizbeth Cornivelli ◽  
Claudio Basilico
Keyword(s):  
Osteoblast Differentiation ◽  
Target Genes ◽  
Expression Profiles ◽  
Constitutive Expression ◽  
Growth Factor Receptor ◽  
Gene Expression Profiles ◽  
Down Regulation ◽  
Activating Mutations ◽  
Proliferation And Differentiation

Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2. Most of these changes could be reproduced by treatment of osteoblasts with exogenous FGF. Wnt signals promote osteoblast function and regulate bone mass. Sox2 is expressed in calvarial osteoblasts in vivo and we show that constitutive expression of Sox2 inhibits osteoblast differentiation and causes down-regulation of the expression of numerous Wnt target genes. Sox2 associates with β-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain. Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt–β-catenin pathway.

scholarly journals Myc stimulates B lymphocyte differentiation and amplifies calcium signaling

2007 ◽  
Vol 179 (4) ◽  
pp. 717-731 ◽  
Author(s):  
Tania Habib ◽  
Heon Park ◽  
Mark Tsang ◽  
Ignacio Moreno de Alborán ◽  
Andrea Nicks ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cell ◽  
Target Genes ◽  
B Lymphocyte ◽  
Nuclear Translocation ◽  
Efflux Pump ◽  
Double Knockout ◽  
Activated T Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell–specific c-/N-myc double-knockout mice and Eμ-myc transgenic mice bred onto genetic backgrounds (recombinase-activating gene 2−/− and Btk−/− Tec−/−) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+–adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes.

scholarly journals ACTH Induces ERK 1/2 Activation in Rat Adrenal Primary Cultures

2008 ◽  
Vol 14 (S3) ◽  
pp. 101-102
Author(s):  
A.R. Rodrigues ◽  
A.M. Gouveia ◽  
J.G. Ferreira ◽  
H. Almeida
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Primary Cultures ◽  
Signalling Pathways ◽  
Tumour Cell Line ◽  
Adrenal Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mitogen Activated Protein ◽  
G Protein Coupled

Adrenocorticotropic hormone (ACTH) is the most potent stimulator of adrenal cortex, acting through the Melanocortin-2 receptor (MC2R). ACTH induces secretion of steroid hormones, critical for the normal stress response and plays also an important role on cell proliferation and differentiation. MC2R is a classical G-Protein coupled receptor (GPCR), thus activating Protein Kinase A (PKA). However, many studies suggested a cross-talk between different signalling pathways and a more complex intracellular network. In fact, in adrenocortical Y1 tumour cell line, ACTH may activate Extracellular Regulated Kinases 1/2 (ERK 1/2), which belong to the Mitogen-Activated Protein Kinases (MAPKs) family. In addition, this pathway was implicated in in vivo proliferation and steroidogenesis as shown by our group. In order to further explore and clarify ACTH signalling mechanisms, we made the present work to establish a model of primary cultures of rat adrenal cells.

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