Abstract
Although in recent years the study of gene expression variation in the absence of genetic or environmental cues or gene expression heterogeneity has intensified considerably, many basic and applied biological fields still remain unaware of how useful the study of gene expression heterogeneity patterns might be for the characterization of biological systems and/or processes. Largely based on the modulator effect chromatin compaction has for gene expression heterogeneity and the extensive changes in chromatin compaction known to occur for specialized cells that are naturally or artificially induced to revert to less specialized states or dedifferentiate, I recently hypothesized that processes that concur with cell dedifferentiation would show an extensive reduction in gene expression heterogeneity. The confirmation of the existence of such trend could be of wide interest because of the biomedical and biotechnological relevance of cell dedifferentiation-based processes, i.e., regenerative development, cancer, human induced pluripotent stem cells, or plant somatic embryogenesis. Here, I report the first empirical evidence consistent with the existence of an extensive reduction in gene expression heterogeneity for processes that concur with cell dedifferentiation by analyzing transcriptome dynamics along forearm regenerative development in Ambystoma mexicanum or axolotl. Also, I briefly discuss on the utility of the study of gene expression heterogeneity dynamics might have for the characterization of cell dedifferentiation-based processes, and the engineering of tools that afforded better monitoring and modulating such processes. Finally, I reflect on how a transitional reduction in gene expression heterogeneity for dedifferentiated cells can promote a long-term increase in phenotypic heterogeneity following cell dedifferentiation with potential adverse effects for biomedical and biotechnological applications.
Highlights
One of the most intriguing aspects of biological systems is that they are prone to vary even in the absence of genetic or environmental cues (Ackermann, 2015; Altschuler & Wu, 2010; Komin & Skupin, 2017; Liu, Francois & Capp, 2016; Symmons & Raj, 2016)
Since transposable elements (TE) activation is known to occur as a consequence of the extensive chromatin relaxation in un/dedifferentiated cells (Feher, 2015; Grafi & Barak, 2015; Macia, Blanco-Jimenez & Garcia-Perez, 2015; Wang & Wang, 2012), TE activations detected in axolotl regenerative development responses might be consistent with the possibility that the formation of the blastema required, at least partially, dedifferentiating cells that undergo extensive chromatin relaxation
The use of transcriptomic analyses for axolotl regenerative development models seems like an adequate place to seek preliminary support for the hypothesized extensive decrease in gene expression heterogeneity for processes that concur with cell dedifferentiation (Díaz-Castillo, 2017b)
Summary
One of the most intriguing aspects of biological systems is that they are prone to vary even in the absence of genetic or environmental cues (Ackermann, 2015; Altschuler & Wu, 2010; Komin & Skupin, 2017; Liu, Francois & Capp, 2016; Symmons & Raj, 2016). Cell dedifferentiation is known to occur in the initial stages of developmental programs activated in response to injury or regenerative development in vertebrates, the formation of masses of undifferentiated cells such as tumors in animals or calli in plants, or the artificial induction of somatic embryogenesis in plants and human pluripotent stem cells for biomedical applications (Li & Belmonte, 2017; Merrell & Stanger, 2016; Sugiyama, 2015; Yamada, Haga & Yamada, 2014)
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