A stem cell-driven lymphoangiogenic switch coordinates tissue regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA510311 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8327682.fastq.gz | Fastqsanger.gz | |||
| SRR8327683.fastq.gz | Fastqsanger.gz | |||
| SRR8327684.fastq.gz | Fastqsanger.gz | |||
| SRR8327685.fastq.gz | Fastqsanger.gz | |||
| SRR8327686.fastq.gz | Fastqsanger.gz |
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Project description:Tissues rely on stem cells (SCs) for homeostasis and wound-repair. SCs reside in specialized microenvironments (niches) whose complexities and roles in orchestrating tissue growth are still unfolding. Here, we identify lymphatic capillaries as critical SC niche components. In skin, lymphatics form intimate networks around the SCs of each hair follicle (HF) during their non-regenerative phase, and remodel upon regeneration. Seeking understanding, we unravel a secretome switch within SCs that controls lymphatic behavior. Resting SCs express Angiopoietin-like 7 (Angptl7), promoting lymphatic drainage. Upon activation, SCs trigger an anti-lympho-angiogenic program, transiently sparking lymphatic dilation and dampened drainage. In mammals, this dynamic aria between SCs and lymphatics is essential for coordinating HFSC behavior and hair regeneration: Upon either depleting lymphatics, silencing Angptl7 or super-activating anti-lympho-angiogenesis, SCs precociously proliferate and HF regeneration becomes asynchronous. In unearthing lymphatic capillaries as a hitherto under-appreciated SC-niche element, we’ve learned how SCs coordinate their activity across a tissue.
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In regard of the two parts, the primary objective of the run-in phase (n=50 patients) with conventional switch of chemotherapy together with the anti-angiogenic agent is the determination of a distinct cytokines and angiogenic factor (CAF) profile during treatment with FOLFOX and bevacizumab, which allows early detection/prediction of progressive disease. The primary objective of the marker-driven randomized part (n=150 patients) with marker-driven switch of antiangiogenic agent and maintenance of chemotherapy is the evaluation of the efficacy of an early marker-driven switch of anti-angiogenic treatment (bevacizumab to aflibercept)
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Project description:Tissues rely on stem cells (SCs) for homeostasis and wound repair. SCs reside in specialized microenvironments (niches) whose complexities and roles in orchestrating tissue growth are still unfolding. Here, we identify lymphatic capillaries as critical SC-niche components. In skin, lymphatics form intimate networks around hair follicle (HF) SCs. When HFs regenerate, lymphatic-SC connections become dynamic. Using a mouse model, we unravel a secretome switch in SCs that controls lymphatic behavior. Resting SCs express angiopoietin-like protein 7 (Angptl7), promoting lymphatic drainage. Activated SCs switch to Angptl4, triggering transient lymphatic dissociation and reduced drainage. When lymphatics are perturbed or the secretome switch is disrupted, HFs cycle precociously and tissue regeneration becomes asynchronous. In unearthing lymphatic capillaries as a critical SC-niche element, we have learned how SCs coordinate their activity across a tissue.
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Project description:A stem cell-driven lymphoangiogenic switch
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Project description:Regeneration is a common strategy for plants to repair their damaged body plans after attack from other organisms or physical assaults. Trees with bark girdling on a large scale will grow new bark within one month and this bark regeneration after girdling system has been proven to be an efficient method to study secondary vascular development as well as plant tissue regeneration in vivo. We herein show the molecular features of differentiating xylem cell fate switch process during secondary vascular tissue (SVT) regeneration in Populus. Based on our data, we propose a working model to illustrate the molecular dynamics underlying xylem cell fate switch process during SVT regeneration, which is significant to understand the pattern formation during the SVTs regeneration and also would shed light on the mechanisms of tissue regeneration in plants. Specific regenerated tissues of Populus at different stages were isolated by tangential cryo-sectioning. Total RNA from cryo-sections representing different regenerating tissues was extracted for Affymetrix Poplar Whole Genome Array hybridization. Five samples (two replicates for each sample) were used for gene expression analysis: differentiating xylem (diX, Stage 0), dedifferentiating xylem cells (deX, Stage I), regenerated phloem (rPh, Stage II), differentiating regenerated cambium (diC, Stage II) and regenerated cambium (rC, Stage III). In addition, one pooled genomic DNA sample from cryo-sections of differentiating xylem from two trees was isolated for DNA hybridization to produce a new CDF file that was used to mask out some potentially cross-hybridizing probesets from the standard Affymetrix Poplar Genome Array. Supplementary file: poplar.cdf
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