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Principal Investigator: Hunter B Fraser
Organization: STANFORD UNIVERSITY
Fiscal Year: 2024
Award: $681,479
Funding agency: National Human Genome Research Institute
Project Summary
Despite a great deal of research, we have discovered surprisingly little about the genetic
basis of uniquely human traits—largely due to the ethical and practical considerations that
severely limit comparisons between humans and other primates. To advance this field, we
have integrated two effective approaches for studying evolution: induced pluripotent stem
(iPS) cells, and interspecific hybrids. iPS cells can be differentiated into a wide range of
cell types in vitro, circumventing many limitations of primate research, while measurement
of allele-specific gene expression in hybrids allows cis-regulatory divergence and gene
expression adaptations to be mapped genome-wide. To combine these approaches, we
have recently generated human/chimpanzee hybrid iPS cells. We propose to characterize
this powerful resource with RNA-seq and cellular phenotyping in diverse cell types,
including cardiomyocytes, motor neurons, hepatocytes, pancreatic progenitors, skeletal muscle,
retinal pigmented epithelium, and skin organoids that include dermis/epidermis, adipose,
cartilage, hair follicles, and more. Our goal is to discover and experimentally validate genes and
genetic variants that have contributed to the evolutionary origin of our species.
Terms: <3-D><3-Dimensional><3D><3D cell culture><3D culture><AD dementia><ASD><ATAC sequencing><ATAC-seq><ATACseq><Acne><Adipose tissue><Affect><Alleles><Allelomorphs><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Assay for Transposase-Accessible Chromatin using sequencing><Autism><Autistic Disorder><Basal Transcription Factor><Basal transcription factor genes><Biology><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Candidate Disease Gene><Candidate Gene><Carcinoma><Cardiac Muscle Cells><Cardiac Myocytes><Cardiocyte><Cartilage><Cartilaginous Tissue><Cas nuclease technology><Causality><Cell Body><Cell Differentiation><Cell Differentiation process><Cell Line><Cell fusion><CellLine><Cells><Chimp><Chimpanzee><Chromatin><Chromosomes><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Corium><Cricetinae><Cutis><Data><Dermis><Disease><Disorder><Early Infantile Autism><Environment><Epidermis><Epithelial cancer><Ethics><Etiology><Evolution><Exposure to><Fatty Tissue><Frog><Ganglia><Gene Action Regulation><Gene Expression><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Gene Transcription><Gene variant><General Transcription Factor Gene><General Transcription Factors><Genes><Genetic><Genetic Imprinting><Genetic Transcription><Genome Mappings><Genomic Imprinting><Goals><Hair Follicle><Hair follicle structure><Hamsters><Hamsters Mammals><Heart Muscle Cells><Heart myocyte><Hepatic Cells><Hepatic Parenchymal Cell><Hepatocyte><High-Throughput RNA Sequencing><Human><Human Genome><Hybrid Cells><Hybrids><In Vitro><Infantile Autism><Kanner's Syndrome><Knowledge><Liver Cells><Lyonization><Malignant Epithelial Neoplasms><Malignant Epithelial Tumors><Maps><Measurement><Methods><Mice><Mice Mammals><Modeling><Modern Man><Motor Cell><Motor Neurons><Murine><Mus><Muscle Fibers><Myotubes><Natural Selections><Neural Ganglion><Organism><Organoids><Outer pigmented layer of retina><Pan Genus><Pan Species><Pancreas><Pancreatic><Parental Imprinting><Pathway interactions><Phenotype><Pigment cell layer of retina><Pigmented layer of retina><Play><Primary Senile Degenerative Dementia><Primates><Primates Mammals><RNA Expression><RNA Seq><RNA sequencing><RNAseq><Radiation Hybrid Map><Radiation Hybrid Mapping><Rana><Regulation><Research><Research Resources><Resources><Retinal Pigment Epithelium><Retinal pigment epithelial cells><Rhabdomyocyte><Rodent><Rodentia><Rodents Mammals><Role><Salmo trutta><Sampling><Schizophrenia><Schizophrenic Disorders><Skeletal Fiber><Skeletal Muscle><Skeletal Muscle Cell><Skeletal Muscle Fiber><Skeletal Myocytes><Skin><Somatic Cell Hybrids><Strains Cell Lines><Structure of retinal pigment epithelium><System><Testing><Trans-Acting Factors><Trans-Activators><Transactivators><Transcript Expression Analyses><Transcript Expression Analysis><Transcription><Transcription Factor Proto-Oncogene><Transcription factor genes><Trout><Voluntary Muscle><X Inactivation><X-Chromosome Inactivation><adipose><allele variant><allelic variant><analyze gene expression><assay for transposase accessible chromatin followed by sequencing><assay for transposase accessible chromatin seq><assay for transposase accessible chromatin sequencing><assay for transposase-accessible chromatin with sequencing><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><candidate identification><cardiomyocyte><causation><cell type><cellular differentiation><cultured cell line><dementia praecox><disease causation><enzyme activity><epithelial carcinoma><ethical><experience><fetal><gene expression analysis><gene expression assay><genetic variant><genome scale><genome-wide><genomewide><genomic variant><human whole genome><hybrid gene><iPS><iPSC><iPSCs><improved><in vitro Model><induced pluripotent cell><induced pluripotent stem cell><inducible pluripotent stem cell><interest><living system><motoneuron><pathway><primary degenerative dementia><progenitor><schizophrenic><senile dementia of the Alzheimer type><social role><three dimensional><three dimensional cell culture><trait><transcription factor><transcriptional profiling><transcriptome sequencing><transcriptomic sequencing><unethical><white adipose tissue><yellow adipose tissue>