Project description:Clinical and genetic heterogeneity associated with retinal diseases makes stem cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 150. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared to peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, though morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as resource for molecular staging of human stem cell-derived retinal organoids.
Project description:Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids.
Project description:Time-series of single-cell RNA-sequencing performed on stem cell derived retinal organoids or post-mortem tissue from the developing and adult retina
Project description:Background: The FACEBASE consortium was established in part to create a central resource for craniofacial researchers. One purpose is to provide a molecular anatomy of craniofacial development. To this end we have used a combination of laser capture microdissection and RNA-Seq to define the gene expression programs driving development of the murine palate. Results: We focused on the E14.5 palate, soon after medial fusion of the two palatal shelves. The palate was divided into multiple compartments, including medial and lateral, as well as oral and nasal, for both the anterior and posterior domains. A total of 25 RNA-Seq datasets were generated. The results provide a comprehensive view of the region specific expression of all transcription factors, growth factors and receptors. Paracrine interactions can be inferred from flanking compartment growth factor/receptor expression patterns. The results are validated primarily through very high concordance with extensive previously published gene expression data for the developing palate. In addition selected immunostain validations were carried out. Conclusions: This report provides an RNA-Seq based atlas of gene expression patterns driving palate development at microanatomic resolution. This FACEBASE resource is designed to fuel discovery by the craniofacial research community. Laser capture microdissection and RNA-seq were used to generate gene expression profiles of different compartments of the mouse E14.5 developing palate
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.
Project description:Background: The FACEBASE consortium was established in part to create a central resource for craniofacial researchers. One purpose is to provide a molecular anatomy of craniofacial development. To this end we have used a combination of laser capture microdissection and RNA-Seq to define the gene expression programs driving development of the murine palate. Results: We focused on the E14.5 palate, soon after medial fusion of the two palatal shelves. The palate was divided into multiple compartments, including medial and lateral, as well as oral and nasal, for both the anterior and posterior domains. A total of 25 RNA-Seq datasets were generated. The results provide a comprehensive view of the region specific expression of all transcription factors, growth factors and receptors. Paracrine interactions can be inferred from flanking compartment growth factor/receptor expression patterns. The results are validated primarily through very high concordance with extensive previously published gene expression data for the developing palate. In addition selected immunostain validations were carried out. Conclusions: This report provides an RNA-Seq based atlas of gene expression patterns driving palate development at microanatomic resolution. This FACEBASE resource is designed to fuel discovery by the craniofacial research community.
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.
Project description:Retina is the fundamental unit of central nervous system, whose development is orchestrated by the intricate crosstalk of diverse RNA species. However, the molecular complexity of neural retina development remains poorly elucidated, limiting the therapy of retinal neurodegenerative diseases. Herein, we performed whole transcriptome sequencing of mouse retina in E14.5, P1, P7, P12, P17 and adult. The circRNA, lncRNA, miRNA and mRNA expression profiles of the developing retina were comprehensively characterized and the differentially expressed RNAs were screened.