Secondary metabolites of Hülle cells mediate protection of fungal reproductive and overwintering structures against fungivorous animals

Fungal Hülle cells with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. In the soil, Hülle cells nurse the overwintering fruiting bodies of Aspergillus nidulans. The genome of A. nidulans harbors genes for the biosynthesis of xanthones. We show that enzymes and metabolites of this biosynthetic pathway accumulate in Hülle cells under the control of the regulatory velvet complex, which coordinates development and secondary metabolism. Deletion strains blocked in the conversion of anthraquinones to xanthones accumulate emodins and are delayed in maturation and growth of fruiting bodies. Emodin represses fruiting body and resting structure formation in other fungi. Xanthones are not required for sexual development but exert antifeedant effects on fungivorous animals such as springtails and woodlice. Our findings reveal a novel role of Hülle cells in establishing secure niches for A. nidulans by accumulating metabolites with antifeedant activity that protect reproductive structures from animal predators.

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Hülle-cell-mediated protection of fungal reproductive and overwintering structures against fungivorous animals

10.1101/2021.03.14.435325 ◽

2021 ◽

Author(s):

Li Liu ◽

Benedict Dirnberger ◽

Oliver Valerius ◽

Enikő Fekete-Szücs ◽

Rebekka Harting ◽

...

Keyword(s):

Stem Cells ◽

Secondary Metabolism ◽

Sexual Development ◽

Biosynthetic Pathway ◽

Fruiting Bodies ◽

Antifeedant Activity ◽

Multipotent Stem Cells ◽

Reproductive Structures ◽

Velvet Complex

AbstractFungal Hülle cells with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. In the soil, Hülle cells nurse the overwintering fruiting bodies of Aspergillus nidulans. The genome of A. nidulans harbors genes for the biosynthesis of xanthones. We show that enzymes and metabolites of this biosynthetic pathway accumulate in Hülle cells under the control of the regulatory velvet complex, which coordinates development and secondary metabolism. Deletion strains blocked in the conversion of anthraquinones to xanthones are delayed in maturation and growth of fruiting bodies. Xanthones are not required for sexual development but exert antifeedant effects on fungivorous animals such as springtails and woodlice. These findings reveal a novel role of Hülle cells in establishing secure niches for A. nidulans by accumulating metabolites with antifeedant activity that protect reproductive structures from animal predators.

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The Role of the Bone Marrow Microenvironment in the Response to Infection

Frontiers in Immunology ◽

10.3389/fimmu.2020.585402 ◽

2020 ◽

Vol 11 ◽

Author(s):

Courtney B. Johnson ◽

Jizhou Zhang ◽

Daniel Lucas

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Immune Cells ◽

Critical Role ◽

Primary Source ◽

Bone Marrow Microenvironment ◽

Future Research ◽

Multipotent Stem Cells ◽

Hematopoietic Stem

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

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Influence of thymectomy on growth of secondary reproductive structures in rats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.206.1.193 ◽

1964 ◽

Vol 206 (1) ◽

pp. 193-197 ◽

Cited By ~ 6

Author(s):

Constance R. Martin

Keyword(s):

Sexual Development ◽

Seminal Vesicles ◽

Thymus Gland ◽

Ventral Prostate ◽

Sham Operation ◽

Rapid Phase ◽

Reproductive Structures ◽

Response To Stress ◽

Long Evans

Ventral prostate glands and seminal vesicles of Long-Evans rats, thymectomized at 6–6 1/2 weeks of age and autopsied 3 weeks later, were significantly heavier than those of sham-operated rats. Values for thymectomized rats were as great as or greater than those for unoperated controls. The influence of thymectomy and sham operation was less pronounced when surgery was performed on rats which had not yet entered or had completed the most rapid phase of sexual development. A possible role of the thymus gland in the response to stress is discussed.

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Biosynthesis of Fusarubins Accounts for Pigmentation of Fusarium fujikuroi Perithecia

Applied and Environmental Microbiology ◽

10.1128/aem.00823-12 ◽

2012 ◽

Vol 78 (12) ◽

pp. 4468-4480 ◽

Cited By ~ 109

Author(s):

Lena Studt ◽

Philipp Wiemann ◽

Karin Kleigrewe ◽

Hans-Ulrich Humpf ◽

Bettina Tudzynski

Keyword(s):

Secondary Metabolites ◽

Gene Cluster ◽

Biosynthetic Pathway ◽

Polyketide Synthase ◽

Biological Function ◽

Fusarium Fujikuroi ◽

Diverse Group ◽

Fruiting Bodies ◽

Content Type ◽

Encoding Gene

ABSTRACTFusarium fujikuroiproduces a variety of secondary metabolites, of which polyketides form the most diverse group. Among these are the highly pigmented naphthoquinones, which have been shown to possess different functional properties for the fungus. A group of naphthoquinones, polyketides related to fusarubin, were identified inFusariumspp. more than 60 years ago, but neither the genes responsible for their formation nor their biological function has been discovered to date. In addition, although it is known that the sexual fruiting bodies in which the progeny of the fungus develops are darkly colored by a polyketide synthase (PKS)-derived pigment, the structure of this pigment has never been elucidated. Here we present data that link the fusarubin-type polyketides to a defined gene cluster, which we designatefsr, and demonstrate that the fusarubins are the pigments responsible for the coloration of the perithecia. We studied their regulation and the function of the single genes within the cluster by a combination of gene replacements and overexpression of the PKS-encoding gene, and we present a model for the biosynthetic pathway of the fusarubins based on these data.

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Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms222011035 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11035

Author(s):

Virinder Kaur Sarhadi ◽

Ravindra Daddali ◽

Riitta Seppänen-Kaijansinkko

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Poor Prognosis ◽

Paracrine Signaling ◽

Mediated Communication ◽

Multipotent Stem Cells ◽

Genetic Complexity ◽

Potential Applications

Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.

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RSP5 Positively Regulates the Osteogenic Differentiation of Mesenchymal Stem Cells by Activating the K63-Linked Ubiquitination of Akt

Stem Cells International ◽

10.1155/2020/7073805 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Changxiang Liang ◽

Guoyan Liang ◽

Xiaoqing Zheng ◽

Yongxiong Huang ◽

Shuaihao Huang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Bone Repair ◽

Multipotent Stem Cells ◽

Cell Therapies ◽

Ubiquitin Protein Ligase ◽

Promising Target ◽

Further Development

Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.

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Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

Stem Cells International ◽

10.1155/2016/3162743 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

R. A. Contreras ◽

F. E. Figueroa ◽

F. Djouad ◽

P. Luz-Crawford

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Multipotent Stem Cells ◽

Immune Systems ◽

Adaptive Immune ◽

Adaptive Immune Systems

Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studiedin vitroandin vivoin experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

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Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/2989076 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 104

Author(s):

Ryan A. Denu ◽

Peiman Hematti

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Cell Biology ◽

Immune Modulation ◽

Ex Vivo ◽

Multipotent Stem Cells ◽

Clinical Potential ◽

Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues.Ex vivoculture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce theirex vivoexpansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSCex vivoexpansion andin vivoengraftment, function, and longevity.

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