How cells progress from stem cells to end-stage differentiation is poorly understood. Substantial evidence indicates that transcriptional regulator networks play a key role in this process. One possibility is that the network regulating differentiation is comprised of a series of switch-like steps that open certain options and preclude others. These switch-like processes emerge from properties of the dynamics of gene regulatory networks. An alternative, not mutually exclusive, hypothesis is that the path to differentiation is a series of incremental steps, each one modifying the output of the gene regulatory network. The latter hypothesis encompasses more tolerance for overlapping differentiation pathways as well as a greater degree of reversibility. These alternative hypotheses will be tested in the tractable model of the Arabidopsis root. The simplicity of its organization, with an accessible stem cell center that gives rise to all the other cells, makes it n ideal model in which to perturb and characterize the differentiation pathway in the context of a developing organ. Regulatory networks that control the asymmetric division of a stem cell population in the root and determine critical steps along the differentiation pathway have been characterized. A mathematical model has been derived to simulate network activity during the asymmetric cell division. Innovative approaches that will be used include the experimental determination of model parameters using fluorescence correlation spectroscopy and monitoring dynamics of network components employing 2-photon light sheet microscopy. Newly identified targets and upstream regulators will be added to the current networks. The design principles of the networks will be tested by targeted perturbations, examining regulators in new cellular contexts and through use of synthetic transcriptional regulators. Knowledge of the process by which the progeny of stem cells become differentiated will be critical to harnessing the power of induced pluripotent stem cells for therapeutic purposes such as tissue regeneration and for providing insight into the dedifferentiated state of tumor cells.
The use of pluripotent stem cells to regenerate damaged tissue is an exciting therapeutic possibility. Knowledge of the process by which the progeny of stem cells become differentiated will be critical to harnessing the power of induced pluripotent stem cells and should provide insight into the dedifferentiated state of tumor cells.
|Verbon, Eline H; Liberman, Louisa M (2016) Beneficial Microbes Affect Endogenous Mechanisms Controlling Root Development. Trends Plant Sci 21:218-29|
|Li, Song; Yamada, Masashi; Han, Xinwei et al. (2016) High-Resolution Expression Map of the Arabidopsis Root Reveals Alternative Splicing and lincRNA Regulation. Dev Cell 39:508-522|
|Hsu, Polly Yingshan; Calviello, Lorenzo; Wu, Hsin-Yen Larry et al. (2016) Super-resolution ribosome profiling reveals unannotated translation events in Arabidopsis. Proc Natl Acad Sci U S A :|
|Clark, Natalie M; Hinde, Elizabeth; Winter, Cara M et al. (2016) Tracking transcription factor mobility and interaction in Arabidopsis roots with fluorescence correlation spectroscopy. Elife 5:|
|Moreno-Risueno, Miguel A; Sozzani, Rosangela; YardÄ±mcÄ±, Galip GÃ¼rkan et al. (2015) Transcriptional control of tissue formation throughout root development. Science 350:426-30|
|Cederholm, Heidi M; Benfey, Philip N (2015) Distinct sensitivities to phosphate deprivation suggest that RGF peptides play disparate roles in Arabidopsis thaliana root development. New Phytol 207:683-91|
|Rodriguez, Ramiro E; Ercoli, MarÃa Florencia; Debernardi, Juan Manuel et al. (2015) MicroRNA miR396 Regulates the Switch between Stem Cells and Transit-Amplifying Cells in Arabidopsis Roots. Plant Cell 27:3354-66|
|Liberman, Louisa M; Sparks, Erin E; Moreno-Risueno, Miguel A et al. (2015) MYB36 regulates the transition from proliferation to differentiation in the Arabidopsis root. Proc Natl Acad Sci U S A 112:12099-104|
|Sozzani, Rosangela; Busch, Wolfgang; Spalding, Edgar P et al. (2014) Advanced imaging techniques for the study of plant growth and development. Trends Plant Sci 19:304-10|
|Sparks, Erin E; Benfey, Philip N (2014) HEC of a job regulating stem cells. Dev Cell 28:349-50|
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