Image copyright Thinkstock 
 
 Plucking hairs in a precise pattern can make even more pop up in their place, a US study suggests. 
 
 Playing with the density of hair removed altered how serious an injury the body recognised and in turn how much hair regrew. 
 
 The team managed to regenerate 1,300 hairs by plucking 200, in the study using mice reported in Cell journal. 
 
 Experts said it was "really nice science" but were uncertain if it could lead to a cure for human baldness. 
 
 Half of men have male-pattern baldness by the age of 50. 
 
 The team at the University of Southern California were investigating how hair follicles communicate with each other to decide on the scale of repair job needed. 
 
 Inflammation 
 
 In a series of experiments they removed 200 hair follicles from a circular patch of skin in mice. 
 
 A low-density pluck - removing follicles from a patch 6mm in diameter - led to no regeneration at all. 
 
 A medium-density pluck, with 200 removed from a 5mm circle, led to 1,300 new hairs. 
 
 A higher-density effort, with the same number of hairs but from a 4mm diameters circle, led to 780 new hairs. 
 
 Pulling every hair out led to every hair coming back, but no extra regeneration. 
 
 Image copyright Cheng-Ming Chuong Image caption Hair comes back thicker after thorough plucking 
 
 The researchers showed that the level of inflammation under the skin was finely tuned to the scale of the damage. 
 
 And through a cascade of chemical signalling and immune responses, this controlled the amount of regeneration. 
 
 The team say it is like each hair gets a vote about what happens next and when it reaches a critical threshold it can trigger regeneration. They call the concept "quorum sensing". 
 
 Lead researcher Dr Cheng-Ming Chuong said: "It is a good example of how basic research can lead to work with potential translational value. 
 
 "The work leads to potential new targets for treating alopecia, a form of hair loss." 
 
 What the findings means for people plucking their eyebrows is uncertain. 
 
 Pathway 
 
 Chris Mason, professor of regenerative medicine at University College London, told the BBC: "It's a really nice piece of science. The idea of quorum sensing is smart." 
 
 But it is not known whether it will cure human baldness. 
 
 Prof Mason added: "That's the million-dollar question. I'm not sure. As it stands here, you've got to have some hair to pluck. 
 
 "A lot of studies have produced hair, but it's too fine - it's baby hair, it's light-coloured and it just doesn't look right. But here we can infer they are adult hairs so that is something that is a step change. 
 
 "Could you tap into the pathway with a cream or injection? That could well be possible - or maybe don't wait until you're totally bald?" 

 Bacteria chatter among themselves. A chemical signaling system called quorum sensing allows those single-celled bugs to detect when their numbers have multiplied enough to mount an effective attack or emit glowing light. Yet decades after scientists learned about this brainless bacterial coordination a research team has uncovered new evidence suggesting animal cells may speak the same lingo. 
 
 
 
 These new hints were revealed through an unexpected approach—plucking hairs. When a researcher at the University of Southern California and his colleagues plucked 200 hairs from mice in a specific pattern in a confined area—ensuring that many neighboring hairs were pulled—more than 1,000 hairs grew back in their place, including some beyond the plucked region. (The mice were anesthetized so they did not feel the hairs being plucked from their bodies.) The findings are published April 9 in Cell. 
 
 
 
 Why didn't the same number of plucked hairs grow back to replace their fallen kin? It appears that hundreds of affected hair follicles released chemical signals relaying distress. Then, once enough neighboring cells sent out similar chemical flares, sensors on the skin detected the messages and took collective action: Incredibly, those messages induced the regeneration of as much as five times the amount of replacement hair. 
 
 
 
 If quorum sensing was behind this action, as the research team suggests, it would represent some of the first evidence to date that this phenomenon occurs in animal cells. Earlier work has suggested quorum sensing may also explain how bees and ants decide on social action as a group. Other studies have indicated that bacteria and cells lining the intestine may interact with one another via this system, too. But this would be the first indication that such signaling can occur across the skin and prompt ample hair regrowth. “It’s a pretty new field, but if cells can signal to bacteria in the gut, as research has shown, you would think they could signal amongst themselves as well,” so these findings make sense, says Julia van Kessel, an assistant research scientist at Indiana University Bloomington who focuses on quorum sensing. 
 
 
 
 Of course, this hair plucking reaction does not mean that if humans start to go bald, plucking a few surrounding hairs would trigger a massive resurgence or that irritating the scalp will necessarily be the key to luscious locks, according to lead author Cheng-Ming Chuong, a professor of pathology at U.S.C. To combat something like male pattern baldness—which is fueled by genes and hormones and involves changes in the hair follicles themselves—much more study would need to take place before researchers could understand how or even if these findings can be translated into therapeutic steps. 
 
 
 
 Still, because the skin cells mounted a massive coordinated response across their population, something was clearly occurring beyond individual hair regeneration, Chuong says. Indeed, when his team plucked a specific number of hairs in a particular circular configuration, it appears that the number and pattern of the plucking events acted as a tipping point to spark that reaction. 
 
 
 
 Chuong's team did not see a similar hair regrowth reaction when it plucked the same number of hairs spread over a larger area. If the plucking pattern exceeded six millimeters in diameter, for example, hairs did not regenerate at all—even after 30 days. Higher-density plucking from circular areas with diameters between three and five millimeters, however, triggered the regeneration of between 450 and 1,300 hairs, including ones outside of the plucked area. The team also detected elevated levels of certain chemicals that suggest the cells were “talking” amongst themselves. “Chemical communication between mammalian cells has obviously been reported before but the novelty here is about space and crowding,” says Vanessa Sperandio, a professor of microbiology and biochemistry who focuses on quorum sensing at The University of Texas Southwestern Medical Center. “There is a relationship here with thresholds that no one has seen before,” says Sperandio, who was not involved with the study. 
 
 
 
 Those chemical signatures were present around the massive hair regeneration spots but not around areas that failed to have this massive regrowth—potential evidence of chemical signaling in quorum sensing, Chuong’s team wrote. Collectively, these clues all suggest neighbor cells’ signaling had some importance. 
 
 
 
 In bacteria it has been widely documented that communication hinges on quorum sensing. When there are only a few bacteria, they will not meet the threshold for action. But once their concentration is high—which they can sense from a greater number of signaling molecules around them—they can and will take collective action. Quorum sensing in animal cells, Chuong says, could similarly help the body decide whether to ignore small irritations or take collective action. “I think quorum sensing would help an organ respond collectively so it could deal with outside stimuli in the most effective and efficient way,” he says. 
 
 
 
 In future research Chuong hopes his team or others will uncover whether a similar communication strategy may occur in other parts of the body or even in other species—including humans. For now, his team studied hairs because it is easy to visualize regeneration and to appreciate the signaling behavior, he says. “In terms of broader significance we think quorum sensing could exist in other organ systems as well,” he adds. Van Kessel, who was not involved with this work, agrees. Although bacteria are easy to work with and have been the main focus of other quorum sensing studies in the past couple decades, “I don’t think quorum sensing is limited to bacteria. It’s just that we’ve always studied them and they are easy to manipulate,” she says. “This is definitely a new way of thinking about things.” 
 
 

 How do cells collectively control an organ’s behavior? By plucking various numbers of hairs from the mouse skin, Chen et al. show that hairs regenerate only when a sufficiently high density of them are plucked. Remarkably, a hair follicle can only regenerate in concert with other follicles, but not autonomously. 
 
 Main Text 
 
 Chen et al. (2015) Chen C.-C. 
 
 Wang L. 
 
 Plikus M.V. 
 
 Jiang T.X. 
 
 Murray P.J. 
 
 Ramos R. 
 
 Guerrero-Juarez C.F. 
 
 Hughes M.W. 
 
 Lee O.K. 
 
 Shi S. 
 
 et al. Cell. 161 ( ) : 277-290 Figure 1 A Hair Follicle Can Only Regenerate in Concert with Other Follicles, but Not by Itself Show full caption (A) When the density of plucked hairs from the mouse skin is lower than a certain density (i.e., “threshold density”), no follicles regenerate. If the density of plucked hairs is higher than the threshold, all the follicles of plucked hairs (“distressed follicles”) and the follicles of surrounding intact hairs (“healthy follicles”) regenerate by entering growth (anagen) phase from a dormant (telogen) phase. (B) A distressed hair follicle secretes the cytokine Ccl2. M1 macrophages sense Ccl2 and swim toward the distressed follicle. (C) Macrophages secrete Tnf-α. Tnf-α activates regeneration of distressed and healthy follicles. Higher density of distressed follicles leads to a higher density of M1 macrophages recruited to the follicles. (D) Main factors that a group of cells may use to collectively make a binary decision. A cell can modify its behavior in response to signaling molecules secreted by its neighboring cells. This cell, in turn, can secrete a signaling molecule that changes its neighboring cells’ behaviors. In a population of cells, such a dynamic back and forth between many cells means that there are often no sharp boundaries between actions of cells that are autonomous and those that influence other cells. This blending of many individuals into one collective entity, often at a macroscopic scale, is a hallmark of multicellular systems like tissues, organs, and populations of bacteria. It also necessitates quantitative analyses to identify the cascades of events that yield collective behaviors of cells. In this issue of Cell,use mathematical models and experiments to reveal that a group of hair follicles can “count” how many hairs have been plucked from the skin and then regenerate the lost hairs if the density of plucked hairs is above a certain density (i.e., “threshold density”) while not regenerating any hairs if the density of plucked hairs is below this threshold density ( Figure 1 A). The authors have thus uncovered a rare example of quorum sensing, which has mainly been studied in bacteria, at the level of a whole organ in a live animal. 
 
 Chen et al. (2015) Chen C.-C. 
 
 Wang L. 
 
 Plikus M.V. 
 
 Jiang T.X. 
 
 Murray P.J. 
 
 Ramos R. 
 
 Guerrero-Juarez C.F. 
 
 Hughes M.W. 
 
 Lee O.K. 
 
 Shi S. 
 
 et al. Cell. 161 ( ) : 277-290 Jahoda and Christiano, 2011 Jahoda C.A. 
 
 Christiano A.M. Cell. 146 : 678-681 Ng and Bassler, 2009 Ng W.L. 
 
 Bassler B.L. Annu. Rev. Genet. 43 : 197-222 studied hairs that grow on the mouse skin. A “hair unit” consists of a hair that protrudes from the skin and its follicle that lies beneath the skin ( Figure 1 A) (). The follicle contains the stem cells from which a new hair can grow. The authors counted and plucked individual hairs from mice. By varying the geometry of regions on the skin from which the hairs were plucked and the number of plucked hairs, the authors discovered two scenarios. When the density of plucked hairs was below a certain threshold density, no follicles regenerated ( Figure 1 A). But when the density of plucked hairs was above the threshold density, both the follicles of the plucked hairs and of the surrounding intact hairs regenerated ( Figure 1 A). Thus, hair follicles are not autonomous. Instead, they collectively decide whether or not to regenerate both the lost and intact hair follicles. This ability of the follicles to measure the density of lost hairs is a form of quorum sensing (), in which a group of cells “measure” its population density and then together launch a collective action (i.e., regeneration of all hairs) only when the density is high enough. Using quorum sensing, the follicles can ignore harmless minor hair losses while using its resources to repair only harmful major hair losses. 
 
 Chen et al. (2015) Chen C.-C. 
 
 Wang L. 
 
 Plikus M.V. 
 
 Jiang T.X. 
 
 Murray P.J. 
 
 Ramos R. 
 
 Guerrero-Juarez C.F. 
 
 Hughes M.W. 
 
 Lee O.K. 
 
 Shi S. 
 
 et al. Cell. 161 ( ) : 277-290 Remarkably,discovered that a field of hair follicles spanning macroscopic distances (i.e., several mm) could quorum sense. Before degrading or being captured by a cell, a typical signaling molecule can travel no more than about 100 μm. Thus, a “distressed” follicle (i.e., a follicle of a plucked hair) can potentially use a signaling molecule to tell its adjacent follicle, which is typically about 100 μm away, of its hair loss. However, using a mathematical model, the authors deduced that follicles could not quorum sense across millimeter distances if they could only communicate with their immediate neighbors. In fact, they found that follicles must secrete a signal that traveled over a distance of 1 mm, at a higher speed than any molecule could achieve. Turning back to the bench, the authors discovered that a distressed follicle recruited M1 macrophages to it by secreting the attractant chemokine CCL2 ( Figure 1 B). Immunostaining revealed that these motile macrophages first accumulated around the distressed follicles and then around the surrounding healthy ones. The macrophages secreted the signaling molecule Tnf-α that stimulated the regeneration of both the healthy and distressed follicles through pathways that remain to be uncovered ( Figure 1 B). Although more work is required, the authors’ data suggest that an appreciable accumulation of macrophages around the distressed follicles most likely occurs only when the density of distressed follicles is above the threshold density ( Figure 1 C). More importantly, the authors show that motile cells, along with signaling molecules, can transmit information over a macroscopic distance between immobile cells. An interesting question for the future is if such coupling between random diffusion of signaling molecules and directed motion of signaling cells may underlie collective behaviors of other organs. 
 
 Ng and Bassler, 2009 Ng W.L. 
 
 Bassler B.L. Annu. Rev. Genet. 43 : 197-222 Pai et al., 2014 Pai A. 
 
 Srimani J.K. 
 
 Tanouchi Y. 
 
 You L. ACS Synth. Biol. 3 : 220-227 De Monte et al., 2007 De Monte S. 
 
 d’Ovidio F. 
 
 Danø S. 
 
 Sørensen P.G. Proc. Natl. Acad. Sci. USA. 104 : 18377-18381 Rotem et al., 2010 Rotem E. 
 
 Loinger A. 
 
 Ronin I. 
 
 Levin-Reisman I. 
 
 Gabay C. 
 
 Shoresh N. 
 
 Biham O. 
 
 Balaban N.Q. Proc. Natl. Acad. Sci. USA. 107 : 12541-12546 An unresolved mystery is what determines the threshold density of hair loss. In microbial cells, the threshold that divides whether every cell or no cell responds to a signaling molecule is primarily determined by the binding affinity of the molecule to its receptor and a positive feedback regulation in a genetic circuit that controls the cells’ response to the signaling molecule (). But, in multicellular systems, it is unclear how coordination of many different factors leads to a threshold and a binary response ( Figure 1 D). In the case of the hair follicles, the short range of signaling mediated by diffusing molecules (e.g., Ccl2 and Tnf-α), the long range of signaling mediated by the motile macrophages, the spatial arrangements of the hair follicles, and the genetic circuits that control each cell’s secretion and response to the different signals must all fit together to set the threshold density of hair loss and a binary multicellular response (i.e., either every follicle or no follicle regenerates) ( Figure 1 D). One possibility is that the macrophages make a binary decision (i.e., either move toward the distressed follicle or not) while the follicles are incapable of making any binary decisions. Another possibility is that a distressed follicle measures the density of macrophages surrounding it in such a way that it only regenerates when there is a sufficiently large density of macrophages. 

 Although it seems counterintuitive, tests indicate that plucked follicles ‘communicate’, causing an immune response that leads to regrowth 
 
 Baldness is often dreaded by men and there are few, if any, satisfactory options for reversing it. Now scientists have discovered a potential solution, after showing that plucking hair out could actually stimulate growth. 
 
 The counterintuitive discovery, in mice, demonstrates a previously unknown method for triggering hair regeneration. Although the work is at an early stage, the authors believe the same process could be helpful for tackling hair loss in men or people with alopecia. 
 
 Philip Murray, of Dundee University and a co-author, said the findings now need to be tested in people. “It would be a bit of a leap of faith to expect this to work in bald men without doing more experiments,” he said. 
 
 The study found that when hairs were plucked in a specific configuration, follicles in the skin were prompted to send out a “distress” signal that led to even more hairs growing back. Plucking our 200 hairs triggered the growth of up to 1,200 replacement hairs in the mice, the study found. 
 
 Tests showed that the plucked follicles signal distress by releasing inflammatory proteins, which cause immune cells to rush to the site. In turn, these send out signals to all neighbouring follicles indicating that it is time to grow more hair. 
 
 “We’ve made a discovery about how hair communicates when it’s distressed,” said Murray. 
 
 The study, published in the journal Cell, showed that the pattern in which the hair was plucked played an important role in the strength of the “distress” signalling process. The researchers tested this by plucking 200 hair follicles, one by one, in different configurations on the back of a mouse. When plucking the hairs in a low-density pattern from an area more than six millimetres across, no hairs regenerated. However, higher-density plucking from circular areas with diameters between three and five millimetres triggered the regeneration of between 450 and 1,300 hairs – and the regeneration sometimes spilled out beyond the plucked area. 
 
 The authors believe that hair follicles do not simply respond individually to being plucked, but also communicate between themselves - something called “quorum sensing” - and effectively make a group decision about the level of immune response that is necessary. In the case of widely spaced plucking, the follicles are too far apart to be able to signal collectively. However, when the damage is tightly packed a more extreme response is mounted, leading to much stronger hair regrowth. 
 
 A potential drawback in balding men might be that their hairs are already too sparsely spaced for the approach to be helpful. 
 
 “It is a good example of how basic research can lead to a work with potential translational value,” said Cheng-Ming Chuong, professor of pathology at the University of Southern California and lead author.
– Hope for bald men? Perhaps. A study suggests that plucking out one's hair could actually trigger the growth of even more. But before anyone starts tearing at his scalp, know that the plucking process has to be done in a specific way—and has thus far only been tested on mice, the Guardian reports. Still, the results, published in the journal Cell, are promising. Scientists say they involve the way hair follicles communicate with each other. The removal of the hair, done right, causes a "distress" signal in the body that leads to an immune response; the body is essentially told to start growing more hair, the Guardian reports. The process worked when mouse hairs were individually removed from a dense patch, a circular area of between 3 and 5 millimeters. In such cases, when 200 hairs were plucked, up to 1,300 grew back—with some even sprouting up outside the plucked area. But when 200 hairs were removed across an area whose diameter was more than 6 millimeters, none returned. The researchers believe that's because the follicle signaling doesn't work across such a wide space. The BBC adds that more isn't more, in this case: The researchers tested pulling out every hair from a specified area, but found that while those hairs grew back, there was no additional growth. The researchers caution the experiments need to be carried out on bald men, and the Guardian notes that even if the approach does work on humans, it would only help balding men who still had the required amount of hair density. The findings are among the first to point to such group signaling, or quorum sensing, in animal cells, as opposed to bacteria, Scientific American reports. (It's not the only lead in the fight against baldness.)