scholarly journals Integrin-alpha-6+ Candidate stem cells are responsible for whole body regeneration in the invertebrate chordate Botrylloides diegensis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Susannah H. Kassmer ◽  
Adam D. Langenbacher ◽  
Anthony W. De Tomaso
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Lineage Tracing ◽  
Whole Body ◽  
Integrin Alpha 6 ◽  
Canonical Wnt ◽  
Botrylloides Diegensis ◽  
Invertebrate Chordate ◽  
Colonial Ascidians

Abstract Colonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Here, we show that during the early stages of WBR in Botrylloides diegensis, proliferation occurs only in small, blood-borne cells that express integrin-alpha-6 (IA6), pou3 and vasa. WBR cannot proceed when proliferating IA6+ cells are ablated with Mitomycin C, and injection of a single IA6+ Candidate stem cell can rescue WBR after ablation. Lineage tracing using EdU-labeling demonstrates that donor-derived IA6+ Candidate stem cells directly give rise to regenerating tissues. Inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation of IA6+ Candidate stem cells, indicating that these two pathways regulate their activation. In conclusion, we show that IA6+ Candidate stem cells are responsible for whole body regeneration and give rise to regenerating tissues.

scholarly journals Integrin-alpha-6+ Stem Cells (ISCs) are responsible for whole body regeneration in an invertebrate chordate

2019 ◽  
Author(s):  
Susannah H. Kassmer ◽  
Adam Langenbacher ◽  
Anthony W. De Tomaso
Keyword(s):  
Stem Cells ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Whole Body ◽  
Proliferating Cells ◽  
Untreated Individual ◽  
Integrin Alpha 6 ◽  
Canonical Wnt ◽  
Botrylloides Diegensis ◽  
Invertebrate Chordate

AbstractColonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Here, we show that during the early stages of WBR in Botrylloides diegensis, proliferation occurs only in small, blood-borne cells that express integrin-alpha-6 (IA6), pou3 and vasa. Ablation of proliferating cells using Mitomycin C (MMC) blocks WBR in vascular fragments, but can be rescued by injection of cycling cells isolated from an untreated individual. Using prospective isolation and limit dilution analyes, we found that FACS-isolated IA6+ stem cells (ISCs) could rescue WBR in MMC treated vascular fragments, even when injecting only a single cell. Lineage tracing using EdU-labeling further revealed that donor-derived ISCs directly give rise to regenerating tissues. Inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation of ISCs, indicating that these two pathways regulate ISC activation.

scholarly journals R-spondin1 regulates muscle progenitor cell fusion through control of antagonist Wnt signaling pathways

2016 ◽  
Author(s):  
Floriane Lacour ◽  
Elsa Vezin ◽  
Florian Bentzinger ◽  
Marie-Claude Sincennes ◽  
Robert D. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Muscle Regeneration ◽  
Muscle Cells ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Canonical Wnt

SUMMARYTissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitution of normal muscle architecture during skeletal muscle regeneration.

scholarly journals Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling

2016 ◽  
Vol 113 (11) ◽  
pp. E1498-E1505 ◽  
Author(s):  
Xinhong Lim ◽  
Si Hui Tan ◽  
Ka Lou Yu ◽  
Sophia Beng Hui Lim ◽  
Roeland Nusse
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Extended Period ◽  
Lineage Tracing ◽  
Hair Cycle ◽  
Cell Potential ◽  
Differentiated Cells ◽  
Hair Follicle Stem Cells

How stem cells maintain their identity and potency as tissues change during growth is not well understood. In mammalian hair, it is unclear how hair follicle stem cells can enter an extended period of quiescence during the resting phase but retain stem cell potential and be subsequently activated for growth. Here, we use lineage tracing and gene expression mapping to show that the Wnt target gene Axin2 is constantly expressed throughout the hair cycle quiescent phase in outer bulge stem cells that produce their own Wnt signals. Ablating Wnt signaling in the bulge cells causes them to lose their stem cell potency to contribute to hair growth and undergo premature differentiation instead. Bulge cells express secreted Wnt inhibitors, including Dickkopf (Dkk) and secreted frizzled-related protein 1 (Sfrp1). However, the Dickkopf 3 (Dkk3) protein becomes localized to the Wnt-inactive inner bulge that contains differentiated cells. We find that Axin2 expression remains confined to the outer bulge, whereas Dkk3 continues to be localized to the inner bulge during the hair cycle growth phase. Our data suggest that autocrine Wnt signaling in the outer bulge maintains stem cell potency throughout hair cycle quiescence and growth, whereas paracrine Wnt inhibition of inner bulge cells reinforces differentiation.

scholarly journals Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daniel Jun-Kit Hu ◽  
Jina Yun ◽  
Justin Elstrott ◽  
Heinrich Jasper
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Migration ◽  
Wnt Signaling ◽  
Intestinal Epithelium ◽  
Enteroendocrine Cells ◽  
Intestinal Stem Cells ◽  
Canonical Wnt Signaling ◽  
Stem Cell Migration ◽  
Canonical Wnt

AbstractTissue regeneration after injury requires coordinated regulation of stem cell activation, division, and daughter cell differentiation, processes that are increasingly well understood in many regenerating tissues. How accurate stem cell positioning and localized integration of new cells into the damaged epithelium are achieved, however, remains unclear. Here, we show that enteroendocrine cells coordinate stem cell migration towards a wound in the Drosophila intestinal epithelium. In response to injury, enteroendocrine cells release the N-terminal domain of the PTK7 orthologue, Otk, which activates non-canonical Wnt signaling in intestinal stem cells, promoting actin-based protrusion formation and stem cell migration towards a wound. We find that this migratory behavior is closely linked to proliferation, and that it is required for efficient tissue repair during injury. Our findings highlight the role of non-canonical Wnt signaling in regeneration of the intestinal epithelium, and identify enteroendocrine cell-released ligands as critical coordinators of intestinal stem cell migration.

scholarly journals Wnt5a Signaling in Normal and Cancer Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Zhou ◽  
Thomas J. Kipps ◽  
Suping Zhang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Target Cells ◽  
Dependent Manner ◽  
Self Renewal ◽  
Surface Receptors ◽  
Canonical Wnt

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

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