Abstract
The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.
Highlights
The cell is the fundamental unit of living organisms
Hooke reported the discovery of cells in plants in 1665 (Hooke, 1665) and named them for their resemblance to the cells inhabited by monks, but it took nearly two centuries for biologists to appreciate their central role in biology
Genetic variants that contribute to disease typically manifest their action through impact in a particular cell types: for example, genetic variants in the IL23R locus increase risk of autoimmune diseases by
Summary
The cell is the fundamental unit of living organisms. Hooke reported the discovery of cells in plants in 1665 (Hooke, 1665) and named them for their resemblance to the cells inhabited by monks, but it took nearly two centuries for biologists to appreciate their central role in biology. A Human Cell Atlas would have a profound impact on biology and medicine by bringing our understanding of anatomy, development, physiology, pathology, intracellular regulation, and intercellular communication to a new level of resolution It would provide invaluable markers, signatures and tools for basic research (facilitating detection, purification and genetic manipulation of every cell type) and clinical applications (including diagnosis, prognosis and monitoring response to therapy). The definition should evolve based on empirical observation Despite these challenges, recent studies in diverse organs – including immune, nervous, and epithelial tissues – support the prospects for comprehensive discovery of cell types, as well as harmonization of genomic, morphological, and functional classifications (Figure 2A–C). Bifurcated trajectories have been reconstructed in the differentiation of embryonic stem cells, T helper cells, and hematopoietic cells
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