What is a Cell Type and How to Define It?

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Jul 22

PMID 35868277

Authors

Hongkui Zeng

Affiliations

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Abstract

Cell types are the basic functional units of an organism. Cell types exhibit diverse phenotypic properties at multiple levels, making them challenging to define, categorize, and understand. This review provides an overview of the basic principles of cell types rooted in evolution and development and discusses approaches to characterize and classify cell types and investigate how they contribute to the organism's function, using the mammalian brain as a primary example. I propose a roadmap toward a conceptual framework and knowledge base of cell types that will enable a deeper understanding of the dynamic changes of cellular function under healthy and diseased conditions.

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References

Lake B, Ai R, Kaeser G, Salathia N, Yung Y, Liu R . Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science. 2016; 352(6293):1586-90. PMC: 5038589. DOI: 10.1126/science.aaf1204. View

Li H, Janssens J, De Waegeneer M, Kolluru S, Davie K, Gardeux V . Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly. Science. 2022; 375(6584):eabk2432. PMC: 8944923. DOI: 10.1126/science.abk2432. View

Hildebrand D, Cicconet M, Torres R, Choi W, Minh Quan T, Moon J . Whole-brain serial-section electron microscopy in larval zebrafish. Nature. 2017; 545(7654):345-349. PMC: 5594570. DOI: 10.1038/nature22356. View

Osseward 2nd P, Pfaff S . Cell type and circuit modules in the spinal cord. Curr Opin Neurobiol. 2019; 56:175-184. PMC: 8559966. DOI: 10.1016/j.conb.2019.03.003. View

Vanlandewijck M, He L, Mae M, Andrae J, Ando K, Del Gaudio F . A molecular atlas of cell types and zonation in the brain vasculature. Nature. 2018; 554(7693):475-480. DOI: 10.1038/nature25739. View

Masland R . The neuronal organization of the retina. Neuron. 2012; 76(2):266-80. PMC: 3714606. DOI: 10.1016/j.neuron.2012.10.002. View

Li Q, Cheng Z, Zhou L, Darmanis S, Neff N, Okamoto J . Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing. Neuron. 2019; 101(2):207-223.e10. PMC: 6336504. DOI: 10.1016/j.neuron.2018.12.006. View

Zhang Z, Zhou J, Tan P, Pang Y, Rivkin A, Kirchgessner M . Epigenomic diversity of cortical projection neurons in the mouse brain. Nature. 2021; 598(7879):167-173. PMC: 8494636. DOI: 10.1038/s41586-021-03223-w. View

Jenett A, Rubin G, Ngo T, Shepherd D, Murphy C, Dionne H . A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012; 2(4):991-1001. PMC: 3515021. DOI: 10.1016/j.celrep.2012.09.011. View

10.

Regev A, Teichmann S, Lander E, Amit I, Benoist C, Birney E . The Human Cell Atlas. Elife. 2017; 6. PMC: 5762154. DOI: 10.7554/eLife.27041. View

11.

Garcia F, Sun N, Lee H, Godlewski B, Mathys H, Galani K . Single-cell dissection of the human brain vasculature. Nature. 2022; 603(7903):893-899. PMC: 9680899. DOI: 10.1038/s41586-022-04521-7. View

12.

Graybuck L, Daigle T, Sedeno-Cortes A, Walker M, Kalmbach B, Lenz G . Enhancer viruses for combinatorial cell-subclass-specific labeling. Neuron. 2021; 109(9):1449-1464.e13. PMC: 8610077. DOI: 10.1016/j.neuron.2021.03.011. View

13.

Pool A, Wang T, Stafford D, Chance R, Lee S, Ngai J . The cellular basis of distinct thirst modalities. Nature. 2020; 588(7836):112-117. PMC: 7718410. DOI: 10.1038/s41586-020-2821-8. View

14.

Svensson V, Beltrame E, Pachter L . A curated database reveals trends in single-cell transcriptomics. Database (Oxford). 2020; 2020. PMC: 7698659. DOI: 10.1093/database/baaa073. View

15.

Helmstaedter M, Briggman K, Turaga S, Jain V, Seung H, Denk W . Connectomic reconstruction of the inner plexiform layer in the mouse retina. Nature. 2013; 500(7461):168-74. DOI: 10.1038/nature12346. View

16.

Stephan T, Burgess S, Cheng H, Danko C, Gill C, Jarvis E . Darwinian genomics and diversity in the tree of life. Proc Natl Acad Sci U S A. 2022; 119(4). PMC: 8795533. DOI: 10.1073/pnas.2115644119. View

17.

Condylis C, Ghanbari A, Manjrekar N, Bistrong K, Yao S, Yao Z . Dense functional and molecular readout of a circuit hub in sensory cortex. Science. 2022; 375(6576):eabl5981. PMC: 9255671. DOI: 10.1126/science.abl5981. View

18.

Hodge R, Bakken T, Miller J, Smith K, Barkan E, Graybuck L . Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019; 573(7772):61-68. PMC: 6919571. DOI: 10.1038/s41586-019-1506-7. View

19.

Cembrowski M, Wang L, Lemire A, Copeland M, DiLisio S, Clements J . The subiculum is a patchwork of discrete subregions. Elife. 2018; 7. PMC: 6226292. DOI: 10.7554/eLife.37701. View

20.

Replogle J, Saunders R, Pogson A, Hussmann J, Lenail A, Guna A . Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq. Cell. 2022; 185(14):2559-2575.e28. PMC: 9380471. DOI: 10.1016/j.cell.2022.05.013. View