SIX3
Homeobox protein SIX3 (Sine oculis homeobox homolog 3)
Publications[править]
Single-cell RNA sequencing (scRNA-seq) is a powerful tool to study heterogeneity and dynamic changes in cell populations. Clustering scRNA-seq is essential in identifying new cell types and studying their characteristics. We develop CellBIC (single Cell BImodal Clustering) to cluster scRNA-seq data based on modality in the gene expression distribution. Compared with classical bottom-up approaches that rely on a distance metric, CellBIC performs hierarchical clustering in a top-down manner. CellBIC outperformed the bottom-up hierarchical clustering approach and other recently developed clustering algorithms while maintaining the hierarchical structure of cells. Importantly, CellBIC identifies type 2 diabetes and age specific β cell signatures characterized by SIX3 and CDH2, respectively.
MeSH Terms
- Aging
- Algorithms
- Antigens, CD
- Cadherins
- Cluster Analysis
- Computational Biology
- Diabetes Mellitus, Type 2
- Gene Expression Profiling
- Genetic Markers
- Humans
- Islets of Langerhans
- Pancreas
- Sequence Analysis, RNA
- Single-Cell Analysis
Intensive efforts are focused on identifying regulators of human pancreatic islet cell growth and maturation to accelerate development of therapies for diabetes. After birth, islet cell growth and function are dynamically regulated; however, establishing these age-dependent changes in humans has been challenging. Here, we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. These profiles revealed distinct proliferative and functional states of islet α cells or β cells and histone modifications underlying age-dependent gene expression changes. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet β cells. SIX2 and SIX3 were sufficient to enhance insulin content or secretion in immature β cells. Our work provides a unique resource to study human-specific regulators of islet cell maturation and function.
MeSH Terms
- Adult
- Aging
- Cell Differentiation
- Cell Separation
- Child
- Child, Preschool
- Chromatin
- Chromatin Immunoprecipitation
- Diabetes Mellitus
- Gene Expression Regulation, Developmental
- Histone Code
- Homeodomain Proteins
- Humans
- Infant
- Insulin-Secreting Cells
- Middle Aged
- Transcription Factors
- Transcriptome
- Young Adult