scholarly journals Release of Notch activity coordinated by IL-1β signalling confers differentiation plasticity of airway progenitors via Fosl2 during alveolar regeneration

2021 ◽  
Author(s):  
Jinwook Choi ◽  
Yu Jin Jang ◽  
Catherine Dabrowska ◽  
Elhadi Iich ◽  
Kelly Evans ◽  
...  
Keyword(s):  
Cell Fate ◽  
Adult Stem Cells ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Secretory Cells ◽  
Alveolar Type ◽  
Fate Decision ◽  
Cell Fate Conversion ◽  
Epigenetic Signatures

While the acquisition of cellular plasticity in adult stem cells is essential for rapid regeneration after tissue injury, little is known about the underlying molecular mechanisms governing this process. Our data reveal the coordination of airway progenitor differentiation plasticity by inflammatory signals during alveolar regeneration. Upon damage, IL-1β signalling-dependent modulation of Jag1/2 expression in ciliated cells results in the inhibition of Notch signalling in secretory cells, which drives reprogramming and acquisition of differentiation plasticity. We identify a core role for the transcription factor Fosl2/Fra2 in secretory cell fate conversion to alveolar type 2 (AT2) cells retaining the distinct genetic and epigenetic signatures of secretory lineages. We furthermore reveal that KDR/FLK-1+ human secretory cells display a conserved capacity to generate AT2 cells via Notch inhibition. Our results demonstrate the functional role of a IL-1β-Notch-Fosl2 axis for the fate decision of secretory cells during injury repair, proposing a new potential therapeutic target for human lung alveolar regeneration.

Regulation of entry into gametogenesis by Ste11: the endless game

2013 ◽  
Vol 41 (6) ◽  
pp. 1673-1678 ◽  
Author(s):  
Jayamani Anandhakumar ◽  
Sylvain Fauquenoy ◽  
Philippe Materne ◽  
Valérie Migeot ◽  
Damien Hermand
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Fundamental Aspect ◽  
Master Regulator ◽  
Proliferation And Differentiation ◽  
Fate Decision ◽  
High Level ◽  
Transcriptional Controls

Sexual reproduction is a fundamental aspect of eukaryotic cells, and a conserved feature of gametogenesis is its dependency on a master regulator. The ste11 gene was isolated more than 20 years ago by the Yamamoto laboratory as a suppressor of the uncontrolled meiosis driven by a pat1 mutant. Numerous studies from this laboratory and others have established the role of the Ste11 transcription factor as the master regulator of the switch between proliferation and differentiation in fission yeast. The transcriptional and post-transcriptional controls of ste11 expression are intricate, but most are not redundant. Whereas the transcriptional controls ensure that the gene is transcribed at a high level only when nutrients are rare, the post-transcriptional controls restrict the ability of Ste11 to function as a transcription factor to the G1-phase of the cell cycle from where the differentiation programme is initiated. Several feedback loops ensure that the cell fate decision is irreversible. The complete panel of molecular mechanisms operating to warrant the timely expression of the ste11 gene and its encoded protein basically mirrors the advances in the understanding of the numerous ways by which gene expression can be modulated.

S1-1 Role of intrinsic and extrinsic determinants in cell fate decision during neural development

1996 ◽  
Vol 25 ◽  
pp. S2
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto ◽  
Masataka Okabe ◽  
Takao Imai ◽  
Shin-Ichi Sakakibara ◽  
...  
Keyword(s):  
Cell Fate ◽  
Neural Development ◽  
Cell Fate Decision ◽  
Fate Decision

Advances and Challenges in Kidney Organoids

2021 ◽  
Vol 16 ◽  
Author(s):  
Vikram Sabapathy ◽  
Gabrielle Costlow ◽  
Rajkumar Venkatadri ◽  
Murat Dogan ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Complex Structures ◽  
Cell Culture Systems ◽  
Epigenetic Signatures ◽  
Kidney Organoids

: The advent of organoids has renewed researcher's interest in in vitro cell culture systems. A wide variety of protocols, primarily utilizing pluripotent stem cells, are under development to improve organoid generation to mimic organ development. The complexity of organoids generated is greatly influenced based on the method used. Understanding the process of kidney organoid formation gives developmental insights into how renal cells form, mature, and interact with the adjacent cells to form specific spatiotemporal structural patterns. This knowledge can bridge the gaps in understanding in vivo renal developmental processes. Evaluating genetic and epigenetic signatures in specialized cell types can help interpret the molecular mechanisms governing cell fate. In addition, development in single-cell RNA sequencing and 3D bioprinting and microfluidic technologies has led to better identification and understanding of a variety of cell types during differentiation and designing of complex structures to mimic the conditions in vivo. While several reviews have highlighted the application of kidney organoids, there is no comprehensive review of various methodologies specifically focusing on the kidney organoids. This review summarizes the updated differentiation methodologies, applications, and challenges associated with kidney organoids. Here we have comprehensively collated all the different variables influencing the organoid generation.

scholarly journals The role of RHOA signaling in trophectoderm cell-fate decision in cattle

2020 ◽  
Vol 528 (4) ◽  
pp. 713-718
Author(s):  
Nanami Kohri ◽  
Hiroki Akizawa ◽  
Sakie Iisaka ◽  
Hanako Bai ◽  
Masashi Takahashi ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Fate Decision ◽  
Fate Decision ◽  
Rhoa Signaling

scholarly journals Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Preetish Kadur Lakshminarasimha Murthy ◽  
Tara Srinivasan ◽  
Matthew S Bochter ◽  
Rui Xi ◽  
Anastasia Kristine Varanko ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Secretory Cells ◽  
Notch Activity ◽  
Crypt Base ◽  
Notch Ligands ◽  
Cell Zone

Notch signalling maintains stem cell regeneration at the mouse intestinal crypt base and balances the absorptive and secretory lineages in the upper crypt and villus. Here we report the role of Fringe family of glycosyltransferases in modulating Notch activity in the two compartments. At the crypt base, RFNG is enriched in the Paneth cells and increases cell surface expression of DLL1 and DLL4. This promotes Notch activity in the neighbouring Lgr5+ stem cells assisting their self-renewal. Expressed by various secretory cells in the upper crypt and villus, LFNG promotes DLL surface expression and suppresses the secretory lineage . Hence, in the intestinal epithelium, Fringes are present in the ligand-presenting ‘sender’ secretory cells and promote Notch activity in the neighbouring ‘receiver’ cells. Fringes thereby provide for targeted modulation of Notch activity and thus the cell fate in the stem cell zone, or the upper crypt and villus.

scholarly journals The Role of Prep1 in the Regulation of Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3639 ◽  
Author(s):  
Giorgia Maroni ◽  
Daniele Panetta ◽  
Raffaele Luongo ◽  
Indira Krishnan ◽  
Federica La Rosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Gene Dosage ◽  
Homeobox Gene ◽  
Fate Decision

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.

scholarly journals Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Financial Burden ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Inflammatory Reactions ◽  
Anti Inflammatory

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

The role of Wnt/b-catenin-signalling for cell fate decision in megakaryopoiesis of the haematopoietic system

2017 ◽  
Vol 53 ◽  
pp. S57
Author(s):  
Burak Hasan Yalcin ◽  
Jadranka Macas ◽  
Eliza Wiercinska ◽  
Patrick Harter ◽  
Malak Fawaz ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Fate Decision ◽  
Fate Decision ◽  
Haematopoietic System

scholarly journals ATM Kinase-Dependent Regulation of Autophagy: A Key Player in Senescence?

2021 ◽  
Vol 8 ◽  
Author(s):  
Venturina Stagni ◽  
Alessandra Ferri ◽  
Claudia Cirotti ◽  
Daniela Barilà
Keyword(s):  
Cell Fate ◽  
Ataxia Telangiectasia ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Premature Aging ◽  
Ataxia Telangiectasia Mutated ◽  
Atm Kinase ◽  
Cellular Environment ◽  
Key Factor

Increasing evidence suggests a strong interplay between autophagy and genomic stability. Recently, several papers have demonstrated a molecular connection between the DNA Damage Response (DDR) and autophagy and have explored how this link influences cell fate and the choice between apoptosis and senescence in response to different stimuli. The aberrant deregulation of this interplay is linked to the development of pathologies, including cancer and neurodegeneration. Ataxia-telangiectasia mutated kinase (ATM) is the product of a gene that is lost in Ataxia-Telangiectasia (A-T), a rare genetic disorder characterized by ataxia and cerebellar neurodegeneration, defects in the immune response, higher incidence of lymphoma development, and premature aging. Importantly, ATM kinase plays a central role in the DDR, and it can finely tune the balance between senescence and apoptosis: activated ATM promotes autophagy and in particular sustains the lysosomal-mitochondrial axis, which in turn promotes senescence and inhibits apoptosis. Therefore, ATM is the key factor that enables cells to escape apoptosis by entering senescence through modulation of autophagy. Importantly, unlike apoptotic cells, senescent cells are viable and have the ability to secrete proinflammatory and mitogenic factors, thus influencing the cellular environment. In this review we aim to summarize recent advances in the understanding of molecular mechanisms linking DDR and autophagy to senescence, pointing out the role of ATM kinase in these cellular responses. The significance of this regulation in the pathogenesis of Ataxia-Telangiectasia will be discussed.

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