scholarly journals Commentary: Genetic Events and Signaling Mechanisms Underlying Schwann Cell Fate in Development and Cancer

Neurosurgery ◽  
2020 ◽  
Author(s):  
Aria M Jamshidi ◽  
Anthony Diaz ◽  
S Shelby Burks ◽  
Allan D Levi
Neurosurgery ◽  
2020 ◽  
Author(s):  
Harish N Vasudevan ◽  
Calixto-Hope G Lucas ◽  
Javier E Villanueva-Meyer ◽  
Philip V Theodosopoulos ◽  
David R Raleigh

Abstract In this review, we describe Schwann cell development from embryonic neural crest cells to terminally differentiated myelinated and nonmyelinated mature Schwann cells. We focus on the genetic drivers and signaling mechanisms mediating decisions to proliferate versus differentiate during Schwann cell development, highlighting pathways that overlap with Schwann cell development and are dysregulated in tumorigenesis. We conclude by considering how our knowledge of the events underlying Schwann cell development and mouse models of schwannoma, neurofibroma, and malignant peripheral nerve sheath tumor can inform novel therapeutic strategies for patients with cancers derived from Schwann cell lineages.


F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 198 ◽  
Author(s):  
Toshihiro Masaki ◽  
Aidan McGlinchey ◽  
Simon R. Tomlinson ◽  
Jinrong Qu ◽  
Anura Rambukkana

Background: Bacterial pathogens can manipulate or subvert host tissue cells to their advantage at different stages during infection, from initial colonization in primary host niches to dissemination. Recently, we have shown that Mycobacterium leprae (ML), the causative agent of human leprosy, reprogrammed its preferred host niche de-differentiated adult Schwann cells to progenitor/stem cell-like cells (pSLC) which appear to facilitate bacterial spread. Here, we studied how this cell fate change influences bacterial retention and transfer properties of Schwann cells before and after reprogramming.Results: Using primary fibroblasts as bacterial recipient cells, we showed that non-reprogrammed Schwann cells, which preserve all Schwann cell lineage and differentiation markers, possess high bacterial retention capacity when co-cultured with skin fibroblasts; Schwann cells failed to transfer bacteria to fibroblasts at higher numbers even after co-culture for 5 days. In contrast, pSLCs, which are derived from the same Schwann cells but have lost Schwann cell lineage markers due to reprogramming, efficiently transferred bacteria to fibroblasts within 24 hours.Conclusions: ML-induced reprogramming converts lineage-committed Schwann cells with high bacterial retention capacity to a cell type with pSLC stage with effective bacterial transfer properties. We propose that such changes in cellular properties may be associated with the initial intracellular colonization, which requires long-term bacterial retention within Schwann cells, in order to spread the infection to other tissues, which entails efficient bacterial transfer capacity to cells like fibroblasts which are abundant in many tissues, thereby potentially maximizing bacterial dissemination. These data also suggest how pathogens could take advantage of multiple facets of host cell reprogramming according to their needs during infection.


2020 ◽  
Vol 4 (1) ◽  
pp. 41-60 ◽  
Author(s):  
Kay F. Macleod

The process of mitophagy, in which mitochondria are selectively turned over at the autophagolysosome, plays a central role in both eliminating dysfunctional mitochondria and reducing mitochondrial mass as an adaptive response to key physiological stresses, such as hypoxia, nutrient deprivation, and DNA damage. Defects in mitophagy have been linked to altered mitochondrial metabolism, production of excess reactive oxygen species and ferroptosis, heightened inflammasome activation, altered cell fate decisions, and senescence, among other cellular consequences. Consequently, functional mitophagy contributes to proper tissue differentiation and repair and metabolic homeostasis, limiting inflammatory responses and modulating tumor progression and metastasis. This review examines the major pathways that control mitophagy, including PINK1-dependent mitophagy and BNIP3/NIX-dependent mitophagy. It also discusses the cellular signaling mechanisms used to sense mitochondrial dysfunction to activate mitophagy and how defective mitophagy results in deregulated tumor cell growth and cancer.


2020 ◽  
Vol 21 (21) ◽  
pp. 8047
Author(s):  
Emmanuel Varlet ◽  
Sara Ovejero ◽  
Anne-Marie Martinez ◽  
Giacomo Cavalli ◽  
Jerome Moreaux

Plasma cells (PC) are the main effectors of adaptive immunity, responsible for producing antibodies to defend the body against pathogens. They are the result of a complex highly regulated cell differentiation process, taking place in several anatomical locations and involving unique genetic events. Pathologically, PC can undergo tumorigenesis and cause a group of diseases known as plasma cell dyscrasias, including multiple myeloma (MM). MM is a severe disease with poor prognosis that is characterized by the accumulation of malignant PC within the bone marrow, as well as high clinical and molecular heterogeneity. MM patients frequently develop resistance to treatment, leading to relapse. Polycomb group (PcG) proteins are epigenetic regulators involved in cell fate and carcinogenesis. The emerging roles of PcG in PC differentiation and myelomagenesis position them as potential therapeutic targets in MM. Here, we focus on the roles of PcG proteins in normal and malignant plasma cells, as well as their therapeutic implications.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 265
Author(s):  
Katarzyna Hnatuszko-Konka ◽  
Aneta Gerszberg ◽  
Izabela Weremczuk-Jeżyna ◽  
Izabela Grzegorczyk-Karolak

The ability to restore or replace injured tissues can be undoubtedly named among the most spectacular achievements of plant organisms. One of such regeneration pathways is organogenesis, the formation of individual organs from nonmeristematic tissue sections. The process can be triggered in vitro by incubation on medium supplemented with phytohormones. Cytokinins are a class of phytohormones demonstrating pleiotropic effects and a powerful network of molecular interactions. The present study reviews existing knowledge on the possible sequence of molecular and genetic events behind de novo shoot organogenesis initiated by cytokinins. Overall, the review aims to collect reactions encompassed by cytokinin primary responses, starting from phytohormone perception by the dedicated receptors, to transcriptional reprogramming of cell fate by the last module of multistep-phosphorelays. It also includes a brief reminder of other control mechanisms, such as epigenetic reprogramming.


2012 ◽  
Vol 4 (8) ◽  
pp. a005975-a005975 ◽  
Author(s):  
N. Perrimon ◽  
C. Pitsouli ◽  
B.-Z. Shilo

2020 ◽  
Author(s):  
Sophie Colombo ◽  
Valérie Petit ◽  
Roselyne Y Wagner ◽  
Delphine Champeval ◽  
Ichiro Yajima ◽  
...  

AbstractThe canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulates Mitf-M transcription, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, while a small number of second wave melanocytes is derived from Schwann-cell precursors (SCPs). We investigated the influence of β-catenin in the development of melanocytes of the first and second waves by generating mice expressing a constitutively active form of β-catenin in cells expressing tyrosinase. Constitutive activation of β-catenin did not affect the development of truncal melanoblasts, but led to a marked hyperpigmentation of the paws. By activating β-catenin at various stages of development (E8.5-E11.5), we showed that the activation of β-catenin in bipotent SCPs favored melanoblast specification at the expense of Schwann cells in the limbs within a specific temporal window. In addition, hyperactivation of the Wnt/β-catenin pathway repressed FoxD3 expression, which is necessary for Schwann cell development, through Mitf-M activation. In conclusion, β-catenin overexpression promotes SCP cell-fate decisions towards the melanocyte lineage.Summary statementActivation of β-catenin in bipotent Schwann-cell precursors during a specific developmental window, induces MITF and represses FoxD3 to promote melanoblast cell fate at the expense of Schwann cells in limbs.


2016 ◽  
Vol 121 (3) ◽  
pp. 325-335 ◽  
Author(s):  
Anup D. Sharma ◽  
Svitlana Zbarska ◽  
Emma M. Petersen ◽  
Mustafa E. Marti ◽  
Surya K. Mallapragada ◽  
...  

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