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Cell lineage tracing is Fate mapping on a single cell level where a single-cell and all of its progeny is traced during development in an organism. This technique has been important in our understanding of embryonic development in different organisms and has allowed us to see that the fate of a cell in early development is conserved among individuals. Much of the information known about development, regeneration, tissue maintenance, stem cells, and tissue repair has come from cell lineage tracing studies.
Methods
[edit]There are several methods for cell lineage tracing. One method involves visually tracking the blastomere and its progeny from the beginning of development to their end targets. Another method involves tagging a blastomere in the early stages of development and locating it at the end of development to see where it and its progeny end up. [1]
Ablation is where a specific cell in the embryo is removed and the tissues and organs missing after development are noted. This method does not provide an actual fate map, but is helpful in giving an idea of normal cell fate.[1]
Genetic lineage tracing uses a Cre-loxP mouse, marker gene, and Cre mutant for labeling the target cell and its progeny, and allows for direct and chronological observation of labelled cells from outside the body. Inducible multi-colored chimeric used in this method allow for multiple cell lineage tracing at once by tagging each cell with different colors. [2]
Retroviral lineage tracing is favored when tracking progenitor progeny. The retrovirus permanently marks all daughter cells, only integrates into cells undergoing the cell cycle, and will not infect cells not of interest.[3]
Other methods for tracking cell lineages include light-microscopy, two-photon microscopy with fluorescent labeling, tissue clearing, and intra-viral techniques are new and allowing for more complex studies.[4]
Application
[edit]Development
[edit]The complete cell lineage of C. elegans has been traced, and parts of the Drosophila melanogaster, Xenopus laevis, and Zebrafish nervous system have been mapped out. Cell lineage tracing of the C. elegans revealed specific cell fates are relatively conserved across species and every cell undergoes a finite amount of divisions. [3]
Retroviral lineage tracing has shown that a single progenitor cell can give rise to many parts of the nervous system. [5] The natural cell fates of many neurons have been identified, and the order of development in the nervous system has been tracked. Cell lineage studies in vivo and in vitro have shown that clones of progenitor cells can be oligodendrocytes, neurons, and astrocytes. [3]
Regeneration in cells
[edit]Cell-lineage tracing of adult lung epithelial cells in control, gain-of-function, and loss-of-function animals has also been used to understand how the adult epithelial cell is maintained, regenerated, and repaired. Cell lineage tracing combined with other analyses such as clonogenic analysis is used to examine the relationship between stem cells and their progenitor cells in various lung models. [6]
Stem cell research
[edit]Multi-color lineage tracing has been used in identifying normal and neoplastic stem cells. Multiple fluorescent markers are added to better track adult stem cells and their progenitors and allows for multiple cell tracing in vivo and observations from outside the animal body. Cancer stem cells can also be confirmed by use of multi-color genetic lineage tracing. [2]
References
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- ^ a b Stent, G S; Weisblat, D A. "Cell Lineage in the Development of Invertebrate Nervous Systems". Annual Review of Neuroscience. 8 (1): 45–70. doi:10.1146/annurev.ne.08.030185.000401.
- ^ a b Ueno, Hiroo (2016-08-01). "Identification of normal and neoplastic stem cells by the multicolor lineage tracing methods". Pathology International. 66 (8): 423–430. doi:10.1111/pin.12425. ISSN 1440-1827.
- ^ a b c Sanes, Dan H.; Reh, Thomas A.; Harris, William A. Determination and differentiation. pp. 77–104. doi:10.1016/b978-0-12-374539-2.00008-2.
- ^ Fink, Juergen; Andersson-Rolf, Amanda; Koo, Bon-Kyoung. "Adult stem cell lineage tracing and deep tissue imaging". BMB Reports. 48 (12): 655–667. doi:10.5483/bmbrep.2015.48.12.249.
- ^ Sanes, Dan H.; Reh, Thomas A.; Harris, William A. Determination and differentiation. pp. 77–104. doi:10.1016/b978-0-12-374539-2.00008-2.
- ^ McQualter, Jonathan L.; Bertoncello, Ivan (2012-05-01). "Concise Review: Deconstructing the Lung to Reveal Its Regenerative Potential". STEM CELLS. 30 (5): 811–816. doi:10.1002/stem.1055. ISSN 1549-4918.