scholarly journals An evolutionary perspective on immunometabolism

Science ◽  
2019 ◽  
Vol 363 (6423) ◽  
pp. eaar3932 ◽  
Author(s):  
Andrew Wang ◽  
Harding H. Luan ◽  
Ruslan Medzhitov
Keyword(s):  
Cell Fate ◽  
Life History Theory ◽  
De Novo ◽  
Building Blocks ◽  
Biological Processes ◽  
Biological Functions ◽  
Cell Fate Decisions ◽  
Ecological Principles ◽  
Proliferation And Differentiation ◽  
Cell Quiescence

Metabolism is at the core of all biological functions. Anabolic metabolism uses building blocks that are either derived from nutrients or synthesized de novo to produce the biological infrastructure, whereas catabolic metabolism generates energy to fuel all biological processes. Distinct metabolic programs are required to support different biological functions. Thus, recent studies have revealed how signals regulating cell quiescence, proliferation, and differentiation also induce the appropriate metabolic programs. In particular, a wealth of new studies in the field of immunometabolism has unveiled many examples of the connection among metabolism, cell fate decisions, and organismal physiology. We discuss these findings under a unifying framework derived from the evolutionary and ecological principles of life history theory.

scholarly journals Exosome complex orchestrates developmental signaling to balance proliferation and differentiation during erythropoiesis

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Skye C McIver ◽  
Koichi R Katsumura ◽  
Elsa Davids ◽  
Peng Liu ◽  
Yoon-A Kang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Biological Processes ◽  
Erythroid Precursor ◽  
Cell Fate Decisions ◽  
Kit Receptor ◽  
Proliferation And Differentiation ◽  
Developmental Signaling ◽  
Erythroid Maturation ◽  
Kinase Expression ◽  
Exosome Complex

Since the highly conserved exosome complex mediates the degradation and processing of multiple classes of RNAs, it almost certainly controls diverse biological processes. How this post-transcriptional RNA-regulatory machine impacts cell fate decisions and differentiation is poorly understood. Previously, we demonstrated that exosome complex subunits confer an erythroid maturation barricade, and the erythroid transcription factor GATA-1 dismantles the barricade by transcriptionally repressing the cognate genes. While dissecting requirements for the maturation barricade in Mus musculus, we discovered that the exosome complex is a vital determinant of a developmental signaling transition that dictates proliferation/amplification versus differentiation. Exosome complex integrity in erythroid precursor cells ensures Kit receptor tyrosine kinase expression and stem cell factor/Kit signaling, while preventing responsiveness to erythropoietin-instigated signals that promote differentiation. Functioning as a gatekeeper of this developmental signaling transition, the exosome complex controls the massive production of erythroid cells that ensures organismal survival in homeostatic and stress contexts.

scholarly journals The Notch pathway regulates both the proliferation and differentiation of follicular cells in the panoistic ovary of Blattella germanica

Open Biology ◽  
2016 ◽  
Vol 6 (1) ◽  
pp. 150197 ◽  
Author(s):  
Paula Irles ◽  
Nashwa Elshaer ◽  
Maria-Dolors Piulachs
Keyword(s):  
Cell Fate ◽  
Ovarian Follicle ◽  
Notch Pathway ◽  
Blattella Germanica ◽  
Active Role ◽  
Follicular Cells ◽  
Cell Fate Decisions ◽  
Proliferation And Differentiation ◽  
Ancestral Function ◽  
Main Components

The Notch pathway is an essential regulator of cell proliferation and differentiation during development. Its involvement in insect oogenesis has been examined in insect species with meroistic ovaries, and it is known to play a fundamental role in cell fate decisions and the induction of the mitosis-to-endocycle switch in follicular cells (FCs). This work reports the functions of the main components of the Notch pathway (Notch and its ligands Delta and Serrate) during oogenesis in Blattella germanica , a phylogenetically basal species with panoistic ovary. As is revealed by RNAi-based analyses, Notch and Delta were found to contribute towards maintaining the FCs in an immature, non-apoptotic state. This ancestral function of Notch appears in opposition to the induction of transition from mitosis to endocycle that Notch exerts in Drosophila melanogaster, a change in the Notch function that might be in agreement with the evolution of the insect ovary types. Notch was also shown to play an active role in inducing ovarian follicle elongation via the regulation of the cytoskeleton. In addition, Delta and Notch interactions were seen to determine the differentiation of the posterior population of FCs. Serrate levels were found to be Notch-dependent and are involved in the control of the FC programme, although they would appear to play no crucial role in panoistic ovary oogenesis.

scholarly journals Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia

2012 ◽  
Vol 209 (4) ◽  
pp. 713-728 ◽  
Author(s):  
Keunwook Lee ◽  
Ki Taek Nam ◽  
Sung Hoon Cho ◽  
Prathyusha Gudapati ◽  
Yoonha Hwang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Notch Signaling ◽  
Cell Fate ◽  
Lymphoblastic Leukemia ◽  
Notch Receptor ◽  
Leukemic Cells ◽  
Cell Fate Decisions ◽  
Proliferation And Differentiation ◽  
Physiological Outcomes

Notch plays critical roles in both cell fate decisions and tumorigenesis. Notch receptor engagement initiates signaling cascades that include a phosphatidylinositol 3-kinase/target of rapamycin (TOR) pathway. Mammalian TOR (mTOR) participates in two distinct biochemical complexes, mTORC1 and mTORC2, and the relationship between mTORC2 and physiological outcomes dependent on Notch signaling is unknown. In this study, we report contributions of mTORC2 to thymic T-cell acute lymphoblastic leukemia (T-ALL) driven by Notch. Conditional deletion of Rictor, an essential component of mTORC2, impaired Notch-driven proliferation and differentiation of pre-T cells. Furthermore, NF-κB activity depended on the integrity of mTORC2 in thymocytes. Active Akt restored NF-κB activation, a normal rate of proliferation, and differentiation of Rictor-deficient pre-T cells. Strikingly, mTORC2 depletion lowered CCR7 expression in thymocytes and leukemic cells, accompanied by decreased tissue invasion and delayed mortality in T-ALL driven by Notch. Collectively, these findings reveal roles for mTORC2 in promoting thymic T cell development and T-ALL and indicate that mTORC2 is crucial for Notch signaling to regulate Akt and NF-κB.

scholarly journals Hyperactive WNT/CTNNB1 signaling induces a competing cell proliferation and epidermal differentiation response in the mouse mammary epithelium

2021 ◽  
Author(s):  
Larissa Mourao ◽  
Amber L. Zeeman ◽  
Katrin E. Wiese ◽  
Anika Bongaarts ◽  
Lieve L. Oudejans ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
De Novo ◽  
Mammary Epithelium ◽  
Mechanistic Explanation ◽  
Tumor Formation ◽  
Epidermal Differentiation ◽  
Cell Proliferation And Differentiation ◽  
Primary Mouse ◽  
Proliferation And Differentiation

In the past forty years, the WNT/CTNNB1 signaling pathway has emerged as a key player in mammary gland development and homeostasis. While also evidently involved in breast cancer, much unclarity continues to surround its precise role in mammary tumor formation and progression. This is largely due to the fact that the specific and direct effects of hyperactive WNT/CTNNB1 signaling on the mammary epithelium remain unknown. Here we use a primary mouse mammary organoid culture system to close this fundamental knowledge gap. We show that hyperactive WNT/CTNNB1 signaling induces competing cell proliferation and differentiation responses. While proliferation is dominant at lower levels of WNT/CTNNB1 signaling activity, higher levels cause reprogramming towards an epidermal cell fate. We show that this involves de novo activation of the epidermal differentiation cluster (EDC) locus and we identify master regulatory transcription factors that likely control the process. This is the first time that the molecular and cellular dose-response effects of WNT/CTNNB1 signaling in the mammary epithelium have been dissected in such detail. Our analyses reveal that the mammary epithelium is exquisitely sensitive to small changes in WNT/CTNNB1 signaling and offer a mechanistic explanation for the squamous differentiation that is observed in some WNT/CTNNB1 driven tumors.

scholarly journals The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination

Blood ◽  
2022 ◽  
Author(s):  
Celine Overbeeke ◽  
Tamar Tak ◽  
Leendert Koenderman
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Continuous Model ◽  
Feedback Loops ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Cellular Kinetics ◽  
Negative Feedback Loops ◽  
Proliferation And Differentiation ◽  
Mature Neutrophil

Neutrophils are the most abundant white blood cell, and differentiate in homeostasis in the bone marrow from hematopoietic stem cells (HSCs) via multiple intermediate progenitor cells into mature cells that enter the circulation. Recent findings support a continuous model of differentiation in the bone marrow of heterogeneous HSCs and progenitor populations. Cell fate decisions both at the level of proliferation and differentiation are enforced through expression of lineage-determining transcription factors (LDTFs) and their interactions, that are influenced by both intrinsic (intracellular) as well as extrinsic (extracellular) mechanisms. Neutrophil homeostasis is subjected to positive feedback loops, stemming from the gut microbiome, as well as negative feedback loops resulting from the clearance of apoptotic neutrophils by mature macrophages. Finally, the cellular kinetics regarding the replenishing of the mature neutrophil pool is discussed in light of recent, contradictory data.

scholarly journals Quantum Biology: An Update and Perspective

2021 ◽  
Vol 3 (1) ◽  
pp. 80-126
Author(s):  
Youngchan Kim ◽  
Federico Bertagna ◽  
Edeline M. D’Souza ◽  
Derren J. Heyes ◽  
Linus O. Johannissen ◽  
...  
Keyword(s):  
Equilibrium State ◽  
Fluorescent Proteins ◽  
Building Blocks ◽  
Living Systems ◽  
Quantum Mechanical ◽  
Biological Processes ◽  
Biological Functions ◽  
Biomolecular Systems ◽  
Quantum Biology ◽  
Quantum Mechanical Effects

Understanding the rules of life is one of the most important scientific endeavours and has revolutionised both biology and biotechnology. Remarkable advances in observation techniques allow us to investigate a broad range of complex and dynamic biological processes in which living systems could exploit quantum behaviour to enhance and regulate biological functions. Recent evidence suggests that these non-trivial quantum mechanical effects may play a crucial role in maintaining the non-equilibrium state of biomolecular systems. Quantum biology is the study of such quantum aspects of living systems. In this review, we summarise the latest progress in quantum biology, including the areas of enzyme-catalysed reactions, photosynthesis, spin-dependent reactions, DNA, fluorescent proteins, and ion channels. Many of these results are expected to be fundamental building blocks towards understanding the rules of life.

WNT signaling in atrial fibrillation

2021 ◽  
pp. 153537022199408
Author(s):  
Carmen Wolke ◽  
Elmer Antileo ◽  
Uwe Lendeckel
Keyword(s):  
Atrial Fibrillation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Heart Development ◽  
Wnt Signaling Pathway ◽  
Cell Fate Decisions ◽  
Proliferation And Differentiation ◽  
Expression Activity ◽  
Signaling Components

The Wnt signaling pathway regulates physiological processes such as cell proliferation and differentiation, cell fate decisions, and stem cell maintenance and, thus, plays essential roles in embryonic development, but also in adult tissue homeostasis and repair. The Wnt signaling pathway has been associated with heart development and repair and has been shown to be crucially involved in proliferation and differentiation of progenitor cells into cardiomyocytes. The investigation of the role of the Wnt signaling pathway and the regulation of its expression/activity in atrial fibrillation has only just begun. The present minireview (I) provides original data regarding the expression of Wnt signaling components in atrial tissue of patients with atrial fibrillation or sinus rhythm and (II) summarizes the current state of knowledge of the regulation of Wnt signaling components’ expression/activity and the contribution of the various levels of the Wnt signal transduction pathway to the processes of the development, maintenance, and progression of atrial fibrillation.

Biological Assembly of Modular Protein Building Blocks as Sensing, Delivery, and Therapeutic Agents

2020 ◽  
Vol 11 (1) ◽  
pp. 35-62 ◽  
Author(s):  
Emily A. Berckman ◽  
Emily J. Hartzell ◽  
Alexander A. Mitkas ◽  
Qing Sun ◽  
Wilfred Chen
Keyword(s):  
Protein Design ◽  
Biomedical Applications ◽  
De Novo ◽  
Building Blocks ◽  
Specific Protein ◽  
Therapeutic Agents ◽  
Biological Functions ◽  
Functional Protein ◽  
Wide Range ◽  
De Novo Protein Design

Nature has evolved a wide range of strategies to create self-assembled protein nanostructures with structurally defined architectures that serve a myriad of highly specialized biological functions. With the advent of biological tools for site-specific protein modifications and de novo protein design, a wide range of customized protein nanocarriers have been created using both natural and synthetic biological building blocks to mimic these native designs for targeted biomedical applications. In this review, different design frameworks and synthetic decoration strategies for achieving these functional protein nanostructures are summarized. Key attributes of these designer protein nanostructures, their unique functions, and their impact on biosensing and therapeutic applications are discussed.

scholarly journals Divergent Dynamics and Functions of ERK MAP Kinase Signaling in Development, Homeostasis and Cancer: Lessons from Fluorescent Bioimaging

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 513 ◽  
Author(s):  
Yu Muta ◽  
Michiyuki Matsuda ◽  
Masamichi Imajo
Keyword(s):  
Cell Fate ◽  
Cellular Responses ◽  
Erk Signaling ◽  
Biological Processes ◽  
Cell Level ◽  
Erk Activation ◽  
Cell Fate Decisions ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Erk Activity

The extracellular signal-regulated kinase (ERK) signaling pathway regulates a variety of biological processes including cell proliferation, survival, and differentiation. Since ERK activation promotes proliferation of many types of cells, its deregulated/constitutive activation is among general mechanisms for cancer. Recent advances in bioimaging techniques have enabled to visualize ERK activity in real-time at the single-cell level. Emerging evidence from such approaches suggests unexpectedly complex spatiotemporal dynamics of ERK activity in living cells and animals and their crucial roles in determining cellular responses. In this review, we discuss how ERK activity dynamics are regulated and how they affect biological processes including cell fate decisions, cell migration, embryonic development, tissue homeostasis, and tumorigenesis.

scholarly journals Rescue of Notch signaling in cells incapable of GDP-l-fucose synthesis by gap junction transfer of GDP-l-fucose in Drosophila

2012 ◽  
Vol 109 (38) ◽  
pp. 15318-15323 ◽  
Author(s):  
Tomonori Ayukawa ◽  
Kenjiroo Matsumoto ◽  
Hiroyuki O. Ishikawa ◽  
Akira Ishio ◽  
Tomoko Yamakawa ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Gap Junction ◽  
Cell Fate ◽  
Molecular Basis ◽  
De Novo ◽  
Biosynthetic Pathways ◽  
Cell Fate Decisions ◽  
Isolated Organs ◽  
Nucleotide Sugars ◽  
Glycan Modification

Notch (N) is a transmembrane receptor that mediates cell–cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-l-fucose as a donor of fucose. The GDP-l-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-d-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-l-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these mutants functioned cell-nonautonomously, and that GDP-l-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-l-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-l-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-l-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.

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