Bulk RNA-seq of fin and body melanocytes and microenvironments
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE158538 | GEO | 2022/01/17
REPOSITORIES: GEO
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Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
2022-01-12 | PXD027968 | Pride
Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
2022-01-17 | GSE181748 | GEO
Project description:Bulk RNA-seq of fin and body melanocytes and microenvironments
| PRJNA665531 | ENA
Project description:scRNA-seq of fin and body zebrafish melanocytes
| PRJNA753151 | ENA
Project description:Proteins of the human hair shaft contain a wealth of information about the coding regions of the person’s genome from whom the hair is derived. Commonly found at crime scenes, hair shafts may thus provide useful forensic evidence if the information they contain can be exploited. Present experiments show that hair shafts from four different anatomic sites are similarly useful in distinguishing individuals by protein profiling. However, the results demonstrated that protein profiles were dependent on anatomic site, indicating that a proper comparison requires matching the sites of origin. The differences in profile offer the prospect of determining the site of origin of hair by comparison with profiles of shafts from other anatomic sites. By contrast, the genetically variant peptides detected in the protein digests, that map to non-synonymous single nucleotide polymorphisms in subject DNA, were detectable regardless of the anatomic origin of the hair shafts. The resulting profiles of genetically variant peptides were more dependent on a subject’s genotype than on the anatomic origin of the hair shaft. Individual identification therefore can be based on peptide profiles regardless of body location. This study demonstrates the utility of proteomic analysis for increasing the forensic value of hair shaft evidence.
2019-04-04 | PXD011732 | Pride
Project description:Little is known about the mechanisms underlying the localization of human melanocytes during embryogenesis, and how the characteristics of melanocytes differ in various body sites. Immunohistochemical studies of biopsy tissue obtained from four different anatomic sites (scalp, back, abdomen, and sole) of 31 aborted fetuses following the approval of the ethics committee for the study of human gene analysis revealed that the melanocyte-associated marker gp100 was expressed earlier in embryogenesis than other melanocyte markers. Human fetal melanocytes are initially localized in the epidermis, and then migrate to the hair buds from the epidermis but not the dermis. In the sole, melanocytes localize in eccrine sweat gland ducts. Cultured fetal melanocytes did not stain positively for any melanocyte markers other than MITF and nestin. When co-cultured with normal human keratinocytes and fibroblasts, fetal melanocytes stained positively for gp100. Gene expression studies indicated that fetal melanocytes were topographically diverse, especially sole-derived melanocytes compared with other melanocytes. Expression of several genes, including CHI3L1 and FGF7, was higher in sole-derived melanocytes. These findings suggest that human fetal melanocytes derived from the sole have different profiles both in vivo and in vitro compared with melanocytes from other sites.
2011-05-01 | GSE24041 | GEO
Project description:Little is known about the mechanisms underlying the localization of human melanocytes during embryogenesis, and how the characteristics of melanocytes differ in various body sites. Immunohistochemical studies of biopsy tissue obtained from four different anatomic sites (scalp, back, abdomen, and sole) of 31 aborted fetuses following the approval of the ethics committee for the study of human gene analysis revealed that the melanocyte-associated marker gp100 was expressed earlier in embryogenesis than other melanocyte markers. Human fetal melanocytes are initially localized in the epidermis, and then migrate to the hair buds from the epidermis but not the dermis. In the sole, melanocytes localize in eccrine sweat gland ducts. Cultured fetal melanocytes did not stain positively for any melanocyte markers other than MITF and nestin. When co-cultured with normal human keratinocytes and fibroblasts, fetal melanocytes stained positively for gp100. Gene expression studies indicated that fetal melanocytes were topographically diverse, especially sole-derived melanocytes compared with other melanocytes. Expression of several genes, including CHI3L1 and FGF7, was higher in sole-derived melanocytes. These findings suggest that human fetal melanocytes derived from the sole have different profiles both in vivo and in vitro compared with melanocytes from other sites. In this study, microarray analyses were performed using cultured fetal melanocytes from 4 different sites (scalp, back, abdomen and sole) obtained at 19 WOG, and newborn normal epidermal melanocyte as a control. RNA purification was performed using an RNeasy Mini kit (Qiagen, Germany) and those 5 samples, were analyzed using GeneChip 1.0 ST Array (Affymetrix, CA, USA).
2011-04-30 | E-GEOD-24041 | biostudies-arrayexpress
Project description:Data set to accompany : Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet. 2006 Jul;2(7):e119. PMID: 16895450 Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression patterns, but the principles that govern their molecular specialization are poorly understood. Spatial organization of cellular differentiation may be achieved by unique specification of each cell type; alternatively, organization may arise by cells interpreting their position along a coordinate system. Here we test these models by analyzing the genome-wide gene expression profiles of primary fibroblast populations from 43 unique anatomical sites spanning the human body. Large-scale differences in the gene expression programs were related to three anatomic divisions: anterior-posterior (rostral-caudal), proximal-distal, and dermal versus nondermal. A set of 337 genes that varied according to these positional divisions was able to group all 47 samples by their anatomic sites of origin. Genes involved in pattern formation, cell-cell signaling, and matrix remodeling were enriched among this minimal set of positional identifier genes. Many important features of the embryonic pattern of HOX gene expression were retained in fibroblasts and were confirmed both in vitro and in vivo. Together, these findings suggest that site-specific variations in fibroblast gene expression programs are not idiosyncratic but rather are systematically related to their positional identities relative to major anatomic axes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2010-07-01 | E-GEOD-5591 | biostudies-arrayexpress
Project description:Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GAB2 as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transduced Gab2-/- bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors PI3K or SHP2. GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph+ hematologic neoplasms. RNA-Seq expression profiling of 6 mouse bone marrow samples: 3 GAB2 WT (+/+) and 3 GAB2 NULL (-/-)
2016-01-17 | E-GEOD-75615 | biostudies-arrayexpress
Project description:Previous studies of zebrafish caudal fin regeneration have shown that multiple genetic programs are moduled through regulatory factors. MicroRNAs are short highly conserved non-coding genes that suppress expression of target genes and thereby control multiple genetic programs. Given their important regulatory roles and evolutionary conservation, we hypothesize that microRNAs define a conserved genetic regulatory circuit important for appendage regeneration. We characterized microRNA expression during zebrafish caudal fin regeneration using small RNA sequencing. The stages of caudal fin regeneration were assayed for mRNA expression using mRNA sequencing. Small RNA and mRNA gene expression profiling during 0 and 4 days post amputation.
2016-06-01 | E-GEOD-74415 | biostudies-arrayexpress