Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells

Plikus, Maksim V.; Baker, Ruth E.; Chen, Chih Chiang; Fare, Clyde; Cruz, Damon de la; Andl, Thomas; Maini, Philip K.; Millar, Sarah E.; Widelitz, Randall B.; Chuong, Cheng Ming

doi:10.1126/science.1201647

Cited by 190 publications

(269 citation statements)

References 16 publications

(40 reference statements)

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“…Many self-regenerating or replacement systems share a common set of functional genes and cellular dynamics -in this respect the dentition is not unique and many factors utilised in tooth development and replacement are also involved in ectodermal unit development and regeneration, such as in the hair [73,74]. Our view of the dental paradox suggests that this conserved system with common genetic and cellular mechanisms that are deep rooted in evolutionary time must have the capacity to allow great shifts in the developmental and therefore morphological diversity of the dentition.…”

Section: Discussionmentioning

confidence: 99%

Evolution and developmental diversity of tooth regeneration

Tucker

Fraser

2014

Seminars in Cell & Developmental Biology

121

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a b s t r a c tThis review considers the diversity observed during both the development and evolution of tooth replacement throughout the vertebrates in a phylogenetic framework from basal extant chondrichthyan fish and more derived teleost fish to mammals. We illustrate the conservation of the tooth regeneration process among vertebrate clades, where tooth regeneration refers to multiple tooth successors formed de novo for each tooth position in the jaws from a common set of retained dental progenitor cells. We discuss the conserved genetic mechanisms that might be modified to promote morphological diversity in replacement dentitions. We review current research and recent progress in this field during the last decade that have promoted our understanding of tooth diversity in an evolutionary developmental context, and show how tooth replacement and dental regeneration have impacted the evolution of the tooth-jaw module in vertebrates.

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Section: Discussionmentioning

confidence: 99%

Evolution and developmental diversity of tooth regeneration

Tucker

Fraser

2014

Seminars in Cell & Developmental Biology

121

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“…First proposed by Alan Turing (1952), over most of their history reaction-diffusion models have offered speculative, how-possibly explanations of biological pattern formation, as the underlying molecular substances and interaction properties were unknown. But nowadays experimental evidence for the presence of activator-inhibitor systems exists, for example the interaction of pigment cells in zebrafish (Nakamasu et al, 2009), palate growth in mice (Economou et al, 2012), and the regeneration of hair stem cells in mice and rabbits (Plikus et al, 2011).…”

Section: Pattern Formation and Spontaneous Symmetry Breakingmentioning

confidence: 99%

Systems biology and the integration of mechanistic explanation and mathematical explanation

Brigandt

2013

Studies in History and Philosophy of Science Part C: Studies in

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The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models-which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation (as the analysis of a whole in terms of its structural parts and their qualitative interactions) have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena (rather than the explanation of quantitative details), where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism's ability to respond to perturbations (beyond its actual operation). I offer general conclusions for philosophical accounts of explanation.

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“…Apart from the intrafollicular role played by the DP on SCs, extrafollicular s.c. adipose tissue affects hfSC activity via BMPs (13), DKK, Sfrp4 (14), and PDGF (15). Furthermore, hfSCs respond to body hormone status (3) and changes in circadian rhythms (16,17).…”

mentioning

confidence: 99%

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation

Kandyba

Leung

Chen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

157

208

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Hair follicles facilitate the study of stem cell behavior because stem cells in progressive activation stages, ordered within the follicle architecture, are capable of cyclic regeneration. To study the gene network governing the homeostasis of hair bulge stem cells, we developed a Keratin 15-driven genetic model to directly perturb molecular signaling in the stem cells. We visualize the behavior of these modified stem cells, evaluating their hair-regenerating ability and profile their molecular expression. Bone morphogenetic protein (BMP)-inactivated stem cells exhibit molecular profiles resembling those of hair germs, yet still possess multipotentiality in vivo. These cells also exhibit up-regulation of Wnt7a, Wnt7b, and Wnt16 ligands and Frizzled (Fzd) 10 receptor. We demonstrate direct transcriptional modulation of the Wnt7a promoter. These results highlight a previously unknown intra-stem cell antagonistic competition, between BMP and Wnt signaling, to balance stem cell activity. Reduced BMP signaling and increased Wnt signaling tilts each stem cell toward a hair germ fate and, vice versa, based on a continuous scale dependent on the ratio of BMP/Wnt activity. This work reveals one more hierarchical layer regulating stem cell homeostasis beneath the stem cell-dermal papilla-based epithelial-mesenchymal interaction layer and the hair follicle-intradermal adipocyte-based tissue interaction layer. Although hierarchical layers are all based on BMP/Wnt signaling, the multilayered control ensures that all information is taken into consideration and allows hair stem cells to sum up the total activators/inhibitors involved in making the decision of activation.hair follicle stem cells | β-catenin | BMPR1A

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Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells

Cited by 190 publications

References 16 publications

Evolution and developmental diversity of tooth regeneration

Evolution and developmental diversity of tooth regeneration

Systems biology and the integration of mechanistic explanation and mathematical explanation

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation

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