Ontology highlight
ABSTRACT:
PROVIDER: PRJNA492994 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Vitiligo patient iPSCs and iPSCs-derived melanocytes
| PRJNA492768 | ENA
Project description:Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel approach for studying human melanocyte development and disease. Here we report that timed exposure to activators of WNT, BMP and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders. Total RNA obtained from embryonic stem cells (ESCs), ESC-derived melanocyte progenitors, ESC-derived mature melanocytes, primary melanocytes, and disease-specific induced pluripotent stem cell-derived melanocytes.
2013-06-01 | E-GEOD-45226 | biostudies-arrayexpress
Project description:Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuals participate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controls of healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem cells into pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions. Total of 40 chips. 10 patients (3 biospies per patient: 1 lesional , 1 perilesional and 1 non lesional) ; 10 healthy volunteers (1biopsy in matched anatomical areas)
2015-10-01 | E-GEOD-65127 | biostudies-arrayexpress
Project description:Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel approach for studying human melanocyte development and disease. Here we report that timed exposure to activators of WNT, BMP and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders. Total RNA obtained from a timecourse of Dual SMAD Inhibition (DSi), Neural Crest (NC), and Melanocyte (BE) differentiation of human embryonic stem cells in triplicate.
2013-06-01 | E-GEOD-45223 | biostudies-arrayexpress
Project description:Vitiligo, an acquired disorder characterized by depigmented skin patches, results from loss of epidermal melanocytes. Etiology of vitiligo is not clearly understood but environmental, biochemical, genetic, and immune factors play a role in its pathogenesis. There is evidence that melanocyte death is perpetuated by an autoimmune response that causes lesions to spread. 4-tertiary butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH) are phenolic compounds that are known as environmental causes of vitiligo. We used microarray to detail the global gene expression that occurs following exposure of melanocytes to 4-TBP or MBEH to identified distinct classes of up-regulated genes that may contribute to melanocyte loss in vitiligo. We show that human melanocytes exposed to 4-TBP and MBEH show increased production of some inflammatory cytokines. Interleukin-6 (IL6) and IL8, in particular, are expressed at the periphery of vitiligo lesions and may contribute to recruitment of immune components to the areas, perpetuating melanocyte loss. Cultured human epidermal melanocytes were treated with 4TBP or MBEH for 3, 6, or 24 hours and gene expression were compared with untreated cells.
2012-12-01 | E-GEOD-31641 | biostudies-arrayexpress
Project description:Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel approach for studying human melanocyte development and disease. Here we report that timed exposure to activators of WNT, BMP and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders.
2013-06-01 | GSE45226 | GEO
Project description:Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel approach for studying human melanocyte development and disease. Here we report that timed exposure to activators of WNT, BMP and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders.
2013-06-01 | GSE45223 | GEO
Project description:Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuaLesionalparticipate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controLesionalof healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem celLesionalinto pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions.
2015-10-01 | GSE65127 | GEO
Project description:Vitiligo, an acquired disorder characterized by depigmented skin patches, results from loss of epidermal melanocytes. Etiology of vitiligo is not clearly understood but environmental, biochemical, genetic, and immune factors play a role in its pathogenesis. There is evidence that melanocyte death is perpetuated by an autoimmune response that causes lesions to spread. 4-tertiary butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH) are phenolic compounds that are known as environmental causes of vitiligo. We used microarray to detail the global gene expression that occurs following exposure of melanocytes to 4-TBP or MBEH to identified distinct classes of up-regulated genes that may contribute to melanocyte loss in vitiligo. We show that human melanocytes exposed to 4-TBP and MBEH show increased production of some inflammatory cytokines. Interleukin-6 (IL6) and IL8, in particular, are expressed at the periphery of vitiligo lesions and may contribute to recruitment of immune components to the areas, perpetuating melanocyte loss.
2012-12-01 | GSE31641 | GEO
Project description:Vitiligo is a skin disease characterized by the destruction of epidermal melanocytes due to oxidative stress and autoimmune response. As the main responder to oxidative stress, keratinocytes facilitate melanocyte loss under oxidative stress by inducing melanocyte death and recruiting antigen-specific CD8+ T cell to skin to destroy melanocytes. It has been proved that keratinocytes secrete abundant functional exosomes, but the role of exosomes secreted from keratinocytes under oxidative stress in vitiligo pathogenesis is unknown. We found that oxidative stress enhanced the secretion of exosomes from keratinocytes. These exosomes (OS-Exos) administration aggravated melanocyte loss and CD8+ T cell infiltration in the epidermis of tail in the vitiligo mouse model, thereby driving vitiligo progression. OS-Exos suppressed the survival of melanocytes while promoting the proliferation and activation of CD8+ T cells in vitro. As miRNAs contained in OS-Exos might be responsible for the functions of OS-Exos on melanocytes and CD8+ T cells, we employed small RNAs-seq analysis to screen miRNAs enriched in OS-Exos as compared to those in Exos (from untreated HaCaT cells). The hierarchical clustering analysis and the volcano plot showed the distinct signatures of known miRNAs as well as novel miRNAs between OS-Exos and Exos. In total, 276 differentially expressed miRNAs were discovered, with 134 and 142 miRNAs displaying significant up- or down-regulation, respectively, in OS-Exos compared with Exos (P<0.05; fold change≥2. The above data suggest that miRNAs enriched in OS-Exos might contribute to the facilitatory role of OS-Exos in vitiligo progression.
2023-10-23 | GSE245757 | GEO