Regulation of Feather Length: FGF/IGF Signaling and NOTCH/YAP Modulation of Progenitor Cell Topology [bulk RNA-seq]
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PROVIDER: PRJNA1203254 | ENA |
REPOSITORIES: ENA
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Project description:The regulation of organ size is a fundamental biological question. This study investigates how feather length is regulated in chickens. We found collar bulge stem cell zones vary in size: main sickle > lesser sickle > contour feathers. During growth, IGF and FGF9 signaling are highly expressed, while BMP, WIF1 and FGF18 increase toward growth termination. Functional assays show that IGF/FGF signaling promotes feather elongation via tyrosine kinase receptor signaling. scRNA-seq analysis reveals accelerated differentiation of keratinocytes in short contour feathers compared to long sickle feathers. In Phoenix chickens, superlong main sickle feathers exhibit specialized stem cell zones with enhanced DLL1 expression and expanded intermediate-layer cell clusters with dynamic interactions involving NOTCH1/DLL1, YAP1, and WNT signaling in progenitor zones in the proximal follicle. Perturbation experiments induce short feather phenotypes arrested at various stages, shedding light on versatile regulatory mechanisms and paving the way for functional control of diverse feather lengths.
2025-08-22 | GSE285384 | GEO
Project description:The regulation of organ size is a fundamental biological question. This study investigates how feather length is regulated in chickens. We found collar bulge stem cell zones vary in size: main sickle > lesser sickle > contour feathers. During growth, IGF and FGF9 signaling are highly expressed, while BMP, WIF1 and FGF18 increase toward growth termination. Functional assays show that IGF/FGF signaling promotes feather elongation via tyrosine kinase receptor signaling. scRNA-seq analysis reveals accelerated differentiation of keratinocytes in short contour feathers compared to long sickle feathers. In Phoenix chickens, superlong main sickle feathers exhibit specialized stem cell zones with enhanced DLL1 expression and expanded intermediate-layer cell clusters with dynamic interactions involving NOTCH1/DLL1, YAP1, and WNT signaling in progenitor zones in the proximal follicle. Perturbation experiments induce short feather phenotypes arrested at various stages, shedding light on versatile regulatory mechanisms and paving the way for functional control of diverse feather lengths.
2025-08-22 | GSE285382 | GEO
Project description:Regulation of Feather Length: FGF/IGF Signaling and NOTCH/YAP Modulation of Progenitor Cell Topology [scRNA-seq]
| PRJNA1203257 | ENA
Project description: Not available
| S-EPMC12372877 | biostudies-literature
Project description:OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in 2 independent cohorts. RESULTS: Sorafenib-acquired resistance tumors showed significant enrichment of T-ICs (164 cells needed to create a tumor) vs. sorafenib-sensitive tumors (13400 cells) and non-treated tumors (1292 cells), p<0.001. Tumors with sorafenib-acquired resistance were enriched with IGF and FGF signaling cascades (FDR<0.05). In vitro, cells derived from sorafenib-acquired resistant tumors and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumor growth and improved survival in sorafenib-resistant tumors. A sorafenib-resistance 175-gene signature was characterized by enrichment of progenitor-cell features, aggressive tumoral traits and predicted poor survival in 2 cohorts (n=442 HCC patients). CONCLUSION: Acquired resistance to sorafenib is driven by tumor initiating cells with enrichment of progenitor markers and activation of IGF and FGF signaling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.
2016-06-16 | GSE73571 | GEO
Project description:OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in 2 independent cohorts. RESULTS: Sorafenib-acquired resistance tumors showed significant enrichment of T-ICs (164 cells needed to create a tumor) vs. sorafenib-sensitive tumors (13400 cells) and non-treated tumors (1292 cells), p<0.001. Tumors with sorafenib-acquired resistance were enriched with IGF and FGF signaling cascades (FDR<0.05). In vitro, cells derived from sorafenib-acquired resistant tumors and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumor growth and improved survival in sorafenib-resistant tumors. A sorafenib-resistance 175-gene signature was characterized by enrichment of progenitor-cell features, aggressive tumoral traits and predicted poor survival in 2 cohorts (n=442 HCC patients). CONCLUSION: Acquired resistance to sorafenib is driven by tumor initiating cells with enrichment of progenitor markers and activation of IGF and FGF signaling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression. Transcriptomic profile of subcutaneous Huh7 cells-derived tumors treated with sorafenib that developed acquired resistance to the drug (n=4), remain responsive to sorafenib (n=3) or were treated with brivanib after development of resistance (n=3). Gene profiling of hepatospheres generated from tumors with acquired resistance to sorafenib (n=3) and non-treated tumors (n=3) was also analyzed.
2016-06-16 | E-GEOD-73571 | biostudies-arrayexpress
Project description:We integrate experimental data and mathematical modelling to unveil how ERK signal duration is relayed to mRNA dynamics. HEK293 cells were transfected with an inducible form of RAF (âRAF1:ER) and induced with tamoxifen (4OHT) or stimulated with different growth factors (EGF, FGF, iGF). Effects of RAF signalling were perturbed subsequently or in parallel with MEK inhibtor U0126, translation inhibtor cycloheximide (CYHX) and actinomycin D (ActD).
2017-04-28 | E-GEOD-72919 | biostudies-arrayexpress
Project description:The feather follicle is a “professional” regenerative organ that undergoes natural cycling and, regeneration after wound plucking. Similar to mammalian hair follicle, dermal papilla (DP) controls feather regeneration, shape, size, and axis. Here we report gene expression profiling for feather DP at different growth stages. For growth phase, we compared gene expression of DP, the ramogenic zone of feather branching epithelium (Erz) and the mesenchymal pulp (Pp). We also compared gene expression of DP at resting phase. To characterize the feather regeneration process, we further profiled gene expression at Day-2 and Day-4 post wound. Our results provide a resource for investigating feather growth and regeneration. Examination of gene expression in dermal papilla (DP) at growth phase and resting phase feather follicle, and during feather regeneration.
2014-01-22 | E-GEOD-42017 | biostudies-arrayexpress
Project description:Even though feather pecking (FP) in laying hens has been extensively studied, a good solution to prevent chickens from this behavior under commercial circumstances has not been found. Selection against FP behavior is possible, but for a more effective selection across different populations, it is necessary to characterize the genetic mechanism associated with this behavior. In this study, we use a high FP selection line, which has been selected for 8 generations. We present evidence of the presence of a major dominant allele affecting the FP behavior by using an argument based on the presence of mixture in the distribution of the observed FP and by studying the evolution of the proportion of very high FP along the sequence of 8 generations. This hypothesis is further supported by the fact that the gene transcription profile of the birds performing high FP differs from the profile of the other birds performing FP (456 genes differentially expressed from a total of 14,077 investigated genes). Keywords: severe feather pecking , selection , modeling , inheritance pattern From each selection line (high feather pecking line, low feather pecking line and control line) 60 animals were randomly selected. Within each line the birds were randomly assigned to a cage of 20. The cages were kept in a randomized block design. Number of samples analyzed in total: 179 (60 high feather pecking line, 60 low feather pecking line, 59 control line samples. Common reference design using total-RNA purified from brain from a single F1 cross between the high and low feather pecking line as reference.
2009-09-22 | E-GEOD-10380 | biostudies-arrayexpress
Project description:The feather follicle is a “professional” regenerative organ that undergoes natural cycling and, regeneration after wound plucking. Similar to mammalian hair follicle, dermal papilla (DP) controls feather regeneration, shape, size, and axis. Here we report gene expression profiling for feather DP at different growth stages. For growth phase, we compared gene expression of DP, the ramogenic zone of feather branching epithelium (Erz) and the mesenchymal pulp (Pp). We also compared gene expression of DP at resting phase. To characterize the feather regeneration process, we further profiled gene expression at Day-2 and Day-4 post wound. Our results provide a resource for investigating feather growth and regeneration.
2014-01-22 | GSE42017 | GEO