Plikus, Maksim - University of California, Irvine - Department of Developmental and Cell Biology

研究领域

omeostasis of many organs largely depends on the activities of tissue-specific stem cells. In the past, a lot of research has been focused on understanding how individual stem cells respond to signals from their micro-environment and decide between remaining quiescent and becoming activated. However, it was unclear if and how thousands of stem cells can coordinate their activities with one another. Recently, we were able to study collective behavior of adult stem cells using the model of hair regeneration. Each hair has a prominent cluster of stem cells. Since there are thousands of hairs on the surface of the skin and skin is flat, together all hair stem cells form a two-dimensional network of clusters. Within this network each stem cell cluster “listens” to competing activating and inhibitory signals and decides between remaining quiescent and becoming activated based on the combined signaling message that it receives. Because the decision making rules are similar for every stem cell cluster, scaling of this behavior across the entire network results in striking patterns of hair regeneration. To this end, we developed a mathematical approach that enables predictive modeling of the hair regeneration patterns. Using predictive power of the model, we showed how key BMP and WNT signaling pathways from the stem cell micro-environment become reused to mediate long-range communication between neighboring hair stem cell clusters. Currently we are interested in the following questions: A) In addition to WNT and BMP, what other key signaling pathways are co-opted to regulate large-scale regeneration of hair stem cells? We are using the predictive computational modeling coupled with in vivo validation experiments to identify new players in the hair stem cell signaling network. B) Does large-scale coordination exist among stem cells in tissues other than skin? We are looking to identify the analogous two- and three-dimensional stem cell networks in other organs. C) Can stem cell coordination be modulated to design more physiologically-relevant stem cell-based therapies?

近期论文

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Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling Plikus MV, Vollmers C, De la Cruz D, Chaix A, Ramos R, Panda S, Chuong CM PNAS 2013, 10: E2106–E2115 Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding Gay D, Kwon O, Zhang Z, Spata M, Plikus MV, Holler P, Ito M, Yang Z Treffeisen E, Kim C, Nace A, Zhang X, Baratono S, Wang F, Ornitz D, Millar SE, Cotsarelis G Self-organizing and stochastic behaviors during the regeneration of hair stem cells Plikus MV, Baker RE, Chen CC, Fare C, de la Cruz D, Andl T, Maini PK, Millar SE, Widelitz R, Chuong CM Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration Plikus MV, Mayer JA, de la Cruz D, Baker RE, Maini PK, Maxson R, Chuong CM Nature 2008, 451: 340-344