Cell types
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Understanding Cell Types: Definitions, Classifications, and Evolution
Evolutionary Definition of Cell Types
Cell types are fundamental units of multicellular organisms, exhibiting extensive diversification, particularly in animals. Recent research proposes an evolutionary definition of cell types, emphasizing the role of the 'core regulatory complex' (CoRC) of transcription factors. These factors are crucial in distinguishing emergent sister cell types, enabling their independent evolution and regulating cell type-specific traits known as apomeres. This evolutionary perspective helps delineate and compare cell types within and between species, providing a roadmap for future research.
Cell Types as Species: A Metaphorical Exploration
The concept of cell types has been likened to species in systematics and evolutionary biology. Historically, cells were classified based on morphology, physiology, or location. However, single-cell transcriptomic studies have revealed fine-scale differences among cells with similar phenotypes, suggesting that cell type variation may be more continuous than discrete. This has led some researchers to question the notion of fixed cell types. The metaphor of "cell types as species" highlights parallels between the two fields, such as the classification challenges and the evolutionary divergence models.
Defining Human Cell Types
Efforts to create comprehensive cell atlases aim to survey cells across the human lifespan, assigning cell types based on molecular features like the transcriptome, epigenome, and proteome. These atlases provide insights into the organization, ontogeny, and evolution of human tissues, and help explore disease susceptibilities and therapy development. However, the phenotypic diversity among cells of the same type raises questions about the definition of a human cell type.
Conceptual Definitions in Mature Organisms
In mature organisms, cell types are traditionally considered hard-wired, with each cell representing the endpoint of a developmental journey from a single fertilized oocyte. However, cells in established tissues can exist in different maturation and activation states and may even convert into other cell types within the same tissue. Thus, a cell type can be defined by both hard-wired characteristics and softer features like morphology, gene expression, location, function, and plasticity.
A Periodic Table of Cell Types
A proposed framework for distinguishing cell types from cell states is the 'periodic table of cell types.' This concept aligns cell types according to their developmental stages, connecting them through a universal axis from stem cells to differentiated cells. Different states of the same cell type are analogous to 'isotopes,' providing a useful tool for predicting new cell types and states and recognizing relationships throughout development and evolution.
Ontology and Taxonomy of Cell Types
An ontology for cell types has been developed, covering prokaryotic, fungal, animal, and plant worlds. This ontology includes over 680 cell types, classified under several generic categories and organized as a directed acyclic graph. It is designed for use in model organism genome and other biological databases, facilitating systematic and accurate characterization of cell types. Additionally, the Cell Taxonomy repository offers a curated collection of cell types and associated markers, encompassing a wide range of species, tissues, and conditions, thus aiding in the understanding of cellular biology.
Mapping Cell Types Across Human Tissues
Single-cell RNA sequencing (scRNA-seq) analyses have mapped individual cell types across various tissues, revealing both tissue-agnostic features and tissue-specific cell states. These studies highlight the need for systematic comparisons of cell types across different tissues to understand shared and variable transcriptional features and their importance for organ function.
Cell Type-Specific Genetic Regulation
Understanding how human genetic variation affects phenotype requires cell type-specific measurements. Recent studies have identified cell type-specific quantitative trait loci (QTLs) from bulk tissue data, mapping these to genetic variants correlated with expression or splicing differences. This approach enhances the precision in linking phenotypes to genetic variation, providing insights into the cellular specificity of genetic effects and their contribution to complex traits.
Conclusion
The study of cell types is a dynamic and evolving field, with significant implications for understanding development, disease, and evolution. By integrating various classification schemes, ontologies, and single-cell analyses, researchers can gain a deeper understanding of cellular diversity and its underlying genetic regulation. This comprehensive approach will continue to refine our knowledge of cell types and their roles in multicellular organisms.
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