News & views (Fig. 1b). When the interactions between birds the behaviour of a non-reciprocal system that Cynthia J. O. Reichhardt and Charles are non-reciprocal, a state can emerge in which is close to its exceptional-point transition — by Reichhardt are in the Theoretical Division, the birds fly in circles (Fig. 1c). The spatial sym- analogy to existing devices that exploit behav- Los Alamos National Laboratory, Los Alamos, metry in this state is restored because the birds iour near ordinary phase transitions (such as a New Mexico 87544, USA. fly in all directions. Importantly, this state has a refrigerator, which repeatedly vaporizes and e-mail: [email protected] chirality — the birds either all fly clockwise or all condenses its coolant). fly anticlockwise — that is stabilized by the many For example, materials could be devel- interactions between the birds. This stabiliza- oped that exhibit one-way elasticity — that tion prevents the system from flipping back and is, in which mechanical waves propagate 1. Ivlev, A. V. et al. Phys. Rev. X 5, 011035 (2015). forth between the two chiralities, which would undisturbed in one direction, but are totally 2. Fruchart, M., Hanai, R., Littlewood, P. B. & Vitelli, V. Nature produce an average chirality of zero. reflected in the opposite direction. Devices 592, 363–369 (2021). Fruchart et al. now show that the emer- could be engineered to produce coherent 3. Vicsek, T., Czirók, A., Ben-Jacob, E., Cohen, I. & Shochet, O. Phys. Rev. Lett. 75, 1226–1229 (1995). gence of the chiral state occurs at a transition phonons, the mechanical equivalent of a laser 4. Bechinger, C. et al. Rev. Mod. Phys. 88, 045006 (2016). between symmetry and broken symmetry beam. And it might be possible to develop 5. Lavergne, F. A., Wendehenne, H., Bauerle, T. & that is controlled by an exceptional point. By mechanical strain cloaking, in which a portion Bechinger, C. Science 364, 70–74 (2019). 6. Chen, Y., Li, X., Scheibner, C., Vitelli, V. & Huang, G. contrast, transitions in systems at equilibrium of a material is fully isolated from vibrations Preprint at https://arxiv.org/abs/2009.07329 (2020). occur at mathematically distinct ‘critical or shocks. 7. Miri, M.-A. & Alu, A. Science 363, eaar7709 (2019). points’ that are associated with the closing of an energy gap, which causes two distinct states Stem cells of the system to have the same energy. The energy of a dynamic system can be described numerically by a mathematical function called a Hamiltonian, and fundamental modes of the Relax to grow more hair system are characterized by vectors known as eigenvectors. The Hamiltonian of a sys- Rui Yi tem that has non-reciprocal interactions is non-Hermitian1, which means that the eigen- A stress hormone has been found to signal through skin cells vectors are not fully independent. When the to repress the activation of hair-follicle stem cells in mice. directions of these eigenvectors are varied by When this signalling is blocked, hair growth is stimulated. changing a control parameter of the system, Stressed humans, watch out. See p.428 two of the eigenvectors can coalesce at an exceptional point. The authors show that in a many-body system, one of the two overlapping modes When American football quarterback Aaron HFSCs are kept in a quiescent state and so do is known as a long-wavelength Goldstone Rodgers told his fans to relax after his team’s not divide3,4. When hair growth is initiated in mode, and is associated with the breaking of poor start one season, little did he know that the next anagen phase, HFSCs are instructed rotational invariance. In the case of a flock of he was also giving a hair-care tip. His advice to divide and produce progenitor cells. These birds, the Goldstone mode corresponds to a is particularly helpful now, after a long pan- progenitors then begin a journey of differenti- uniform movement of all birds along the flock- demic year. About one-quarter of people who ation, generating several layers of hair follicles ing direction, whereas other modes control contract COVID-19 experience hair loss six and, ultimately, the hair shaft. the relative motion of birds within the flock months after the onset of symptoms1, prob- Since HFSCs were identified in the bulge with respect to each other. ably because of the systemic shock caused by region more than 30 years ago5–7, many regu- At the exceptional point, the complete the ordeal of infection and recovery. Chronic latory molecules — such as gene-transcription overlap of the Goldstone mode with one of the stress has long been associated with hair loss, factors and signalling proteins — have been other modes allows the system to freely switch but the underlying mechanism that links stress shown to control the cells’ quiescence and between all possible ground states, instead of to the dysfunction of hair-follicle stem cells activation3,4. Nearly all of these regulators remaining trapped in one state. For the birds, has been elusive. On page 428, Choi et al.2 are produced by either HFSCs or their neigh- this corresponds to the emergence of chiral uncover the connection in mice. bouring cells, including dermal papilla cells, rotation across the entire system. In other Throughout a person’s lifespan, hair growth which usually function as a supportive ‘niche’ words, Fruchart et al. report how symmetry cycles through three stages: growth (anagen), for HFSCs8,9. But how systemic conditions such that was spontaneously broken on one side degeneration (catagen) and rest (telogen). as chronic stress affect the activity of HFSCs is of the exceptional point can be dynamically During anagen, a hair follicle continuously incompletely understood. restored. pushes out a growing hair shaft. During cata- To answer this question, Choi and col- Although exceptional points have received gen, hair growth stops and the lower portion leagues first tested the role of adrenal glands considerable attention in photonics7, where of the hair follicle shrinks, but the hair (now — which produce stress hormones and con- they have been shown to describe properties known as a club hair) remains in place. Dur- stitute a key endocrine organ — in the regu- such as the one-way transmission of light ing telogen, the club hair remains dormant lation of hair growth, by surgically removing through a material, Fruchart and colleagues for some time, eventually falling out. Under them from mice. Telogen phases were much expand their use to many-body systems that severe stress, many hair follicles enter telogen shorter in the hair follicles of these animals are out of equilibrium. Indeed, the authors’ prematurely and the hair quickly falls out. (which the team dubbed ADX mice) than in findings apply to any system containing two Hair-follicle stem cells (HFSCs) are located control mice (less than 20 days compared key ingredients: non-reciprocal interactions in a region of the hair follicle called the bulge. with 60–100 days), and the follicles engaged in and a spontaneously broken continuous sym- These cells have a crucial role in governing hair growth roughly three times as often. The metry. This opens up the possibility of engi- hair growth by interpreting both internal and authors were able to suppress this frequent neering devices whose function depends on external signals. For example, during telogen, hair growth and restore the normal hair cycle 356 | Nature | Vol 592 | 15 April 2021 ©2021 Spri nger Nature Li mited. All rights reserved. ©2021 Spri nger Nature Li mited. All rights reserved. Figure 1 | Stress and hair growth in mice. a, Hair is generated from hair follicle stem cells (HFSCs), which seem to reside in the bulge and germ regions of structures called follicles, supported by neighbouring dermal papilla cells. Choi et al.2 have discovered a pathway in mice that modulates this process in response to stress. b, Chronic stress causes mice to produce the hormone corticosterone. The authors show that corticosterone binds to the glucocorticoid receptor protein on dermal papillae cells, which leads to a block in production of the protein GAS6. GAS6 would normally activate the AXL receptor protein on HFSCs — its absence means that no activation signal is passed to HFSCs, and no genes associated with the cell cycle are activated. The hair remains in a prolonged ‘telogen’ phase, in which it does not grow. c, When GAS6 is injected into the skin using a viral vector (vector not shown), it can bind to AXL on HFSCs, triggering expression of genes involved in cell division. The HFSCs multiply, and hair growth follows. by feeding the ADX mice cortico sterone (a stress hormone normally produced by the ani- a b Chronic stress Cell-cycle Hair mals’ adrenal glands). Interestingly, when they genes unpredictably applied various mild stressors No HFSC division Prolonged telogen to normal mice for nine weeks, they observed Corticosterone Gas6 elevated corticosterone levels accompanied HFSC by reduced hair growth, supporting the idea AXL that corticosterone produced by the adre- Glucocorticoid nal glands during chronic stress inhibits the receptor DP cell initiation of hair growth. How do HFSCs sense corticosterone? c Chronic stress + GAS6 delivery Because corticosterone signals through a Bulge protein known as the glucocorticoid receptor, HFSC division Hair growth selective deletion of this receptor in different HFSC cell types in the skin should reveal which cells are required to receive the signal. Choi et al. Germ GAS6 found that selective deletion in the dermal papillae blocked the inhibitory effects of corti- DP cell costerone on hair growth, whereas deletion in HFSCs themselves had no effect. This suggests Figure 1 | Stress and hair growth in mice. a, Hair is generated from hair-follicle stem cells (HFSCs), which that HFSCs do not sense the stress hormone are thought to reside in the bulge and germ region of hair follicles during a ‘resting’ phase of hair growth directly — and that, instead, the dermal papil- called telogen.