scholarly journals Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage

2020 ◽  
Author(s):  
Sophie Colombo ◽  
Valérie Petit ◽  
Roselyne Y Wagner ◽  
Delphine Champeval ◽  
Ichiro Yajima ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Fate ◽  
Active Form ◽  
Cell Lineage ◽  
Cell Fate Decisions ◽  
Schwann Cell Development ◽  
Summary Statement ◽  
Schwann Cell Precursors ◽  
Canonical Wnt

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.

scholarly journals Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage

Development ◽  
2021 ◽  
Author(s):  
Sophie Colombo ◽  
Valérie Petit ◽  
Roselyne Y. Wagner ◽  
Delphine Champeval ◽  
Ichiro Yajima ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Cell Fate ◽  
Active Form ◽  
Cell Lineage ◽  
Temporal Window ◽  
Cell Fate Decisions ◽  
Cell Lineages ◽  
Canonical Wnt ◽  
Second Wave

The 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 the second wave of 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 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. Furthermore, in vitro hyperactivation of the Wnt/β-catenin pathway, which is required for melanocyte development, induces activation of Mitf-M, in turn repressing FoxD3 expression. In conclusion, β-catenin overexpression promotes SCP cell fate decisions towards the melanocyte lineage.

scholarly journals Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 198 ◽  
Author(s):  
Toshihiro Masaki ◽  
Aidan McGlinchey ◽  
Simon R. Tomlinson ◽  
Jinrong Qu ◽  
Anura Rambukkana
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Fate ◽  
Cell Lineage ◽  
Mycobacterium Leprae ◽  
Differentiation Markers ◽  
Primary Host ◽  
Transfer Property ◽  
Retention Capacity ◽  
Transfer Properties

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.

scholarly journals Retracing Schwann cell developmental transitions in embryonic dissociated DRG cultures

2020 ◽  
Author(s):  
Venkat Krishnan Sundaram ◽  
Rasha Barakat ◽  
Charbel Massaad ◽  
Julien Grenier
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Reference Genes ◽  
Expression Profiles ◽  
Cell Development ◽  
Developmental Genes ◽  
Developmental Transitions ◽  
Schwann Cell Development ◽  
Schwann Cell Precursors

AbstractEmbryonic Dissociated Dorsal Root Ganglia cultures are often used to investigate the role of novel molecular pathways or drugs in Schwann cell development and myelination. These cultures largely recapitulate the order of cellular and molecular events that occur in Schwann cells of embryonic nerves. However, the timing of Schwann cell developmental transitions, notably the transition from Schwann Cell Precursors to immature Schwann cells, has not been estimated so far in this culture system. In this study, we use RTqPCR to determine the expression profiles of Schwann cell developmental genes during the first week of culture. We first identified stable reference genes that show minimal variation across different experimental time points. Consequently, we normalized the mRNA profiles of Schwann cell developmental genes using the best internal reference genes. We then compared our data to the expression profiles of these genes in developing spinal nerves elaborated in numerous high-throughput and lineage tracing studies. This comparison helped in identifying that Schwann Cell Precursors transition into immature Schwann Cells between the 5th and 7th day in vitro. In effect, our data allows for a better understanding and interpretation of DRG culture experiments especially in studies that aim to elucidate the role of a novel gene in Schwann Cell development and myelination.

scholarly journals Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tim Liebisch ◽  
Armin Drusko ◽  
Biena Mathew ◽  
Ernst H. K. Stelzer ◽  
Sabine C. Fischer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Cell Fate ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Chemical Signalling ◽  
Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

scholarly journals Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Elisa Dorantes-Acosta ◽  
Rosana Pelayo
Keyword(s):  
Cell Fate ◽  
High Efficiency ◽  
Current Knowledge ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Cell Lineage ◽  
Leukemic Cells ◽  
Acute Leukemias ◽  
Cell Fate Decisions ◽  
Lineage Switch

Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.

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

Neurosurgery ◽  
2020 ◽  
Author(s):  
Harish N Vasudevan ◽  
Calixto-Hope G Lucas ◽  
Javier E Villanueva-Meyer ◽  
Philip V Theodosopoulos ◽  
David R Raleigh
Keyword(s):  
Schwann Cell ◽  
Cell Fate ◽  
Cell Development ◽  
Nerve Sheath Tumor ◽  
Cell Lineages ◽  
Nerve Sheath ◽  
Signaling Mechanisms ◽  
Schwann Cell Development ◽  
Novel Therapeutic Strategies ◽  
Genetic Events

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.

scholarly journals Directly induced human Schwann cell precursors as a valuable source of Schwann cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Han-Seop Kim ◽  
Jae Yun Kim ◽  
Cho Lok Song ◽  
Ji Eun Jeong ◽  
Yee Sook Cho
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Valuable Source ◽  
Schwann Cell Precursors
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