{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:50:00Z","timestamp":1787014200058,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human scalp hair follicles (HF) preferentially engage in glycolysis followed by lactate production in the presence of oxygen (i.e. the Warburg effect). Through the spatiotemporally controlled expression of key metabolic proteins, we hypothesise that the Warburg effect and other HF metabolic programmes are compartmentalised by region in order to regulate regional cell fate and phenotypes, such as epithelial stem cell quiescence in the bulge or keratinocyte proliferation in the hair matrix. We further propose that metabolic conditions in the HF are organised in accordance with the lactate shuttle, hypothesised to occur in other tissue systems and tumours, but never before described in the HF. Specifically, we argue that lactate is produced and exported by glycolytic GLUT1+ lower outer root sheath (ORS) keratinocytes. We further propose that lactate is then utilised by neighbouring highly proliferative matrix keratinocytes to fuel oxidative metabolism via MCT1\u2010mediated uptake. Furthermore, as lactate has been described to be immunomodulatory, its production and accumulation could enhance immune tolerance in the HF bulb. Here we delineate how to experimentally probe this hypothesis, define major open questions and present preliminary immunohistological evidence in support of metabolic compartmentalisation and lactate shuttling. Overall, we argue that basic and translational hair research needs to rediscover the importance of lactate in human HF biology, well beyond its recognised role in murine HF epithelial stem cells, and should explore how HF metabolism can be therapeutically targeted to modulate hair growth and the immunological HF microenvironment as a novel strategy for managing hair loss disorders.<\/jats:p>","DOI":"10.1111\/exd.14300","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T10:07:33Z","timestamp":1612606053000},"page":"645-651","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Compartmentalised metabolic programmes in human anagen hair follicles: New targets to modulate epithelial stem cell behaviour, keratinocyte proliferation and hair follicle immune status?"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-7735","authenticated-orcid":false,"given":"Talveen S.","family":"Purba","sequence":"first","affiliation":[{"name":"Centre for Dermatology Research School of Biological Sciences University of Manchester &amp; NIHR Biomedical Research Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u00efla","family":"Berriche","sequence":"additional","affiliation":[{"name":"Centre for Dermatology Research School of Biological Sciences University of Manchester &amp; NIHR Biomedical Research Centre Manchester UK"},{"name":"Claude Bernard Lyon 1 Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-9358","authenticated-orcid":false,"given":"Ralf","family":"Paus","sequence":"additional","affiliation":[{"name":"Centre for Dermatology Research School of Biological Sciences University of Manchester &amp; NIHR Biomedical Research Centre Manchester UK"},{"name":"Monasterium Laboratory M\u00fcnster Germany"},{"name":"Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12476744"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0172-2"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.008"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0259-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0406-2"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00052"},{"key":"e_1_2_12_8_1","first-page":"52","article-title":"Lactate: the ugly duckling of energy metabolism","volume":"7","author":"Rabinowitz JD","year":"2020","journal-title":"Nat Metab"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01961"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.02208"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.11.062"},{"issue":"12","key":"e_1_2_12_12_1","first-page":"3930","article-title":"Targeting lactate\u2010fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux P","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.04.028"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.08.011"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.09.014"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14155"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3575"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.08.011"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13046"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2017.03.011"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15038-9"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/JID.2015.354"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201300166"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12700"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26043"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44478"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4233"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.03.007"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2017.06.008"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.04.004"},{"issue":"7","key":"e_1_2_12_32_1","first-page":"566","article-title":"Metabolic regulation of cell growth and proliferation","volume":"30","author":"Zhu J","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2015.1090068"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13922"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.01.015"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094260"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18854"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12836"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.02.024"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799504902"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-2270"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003705"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05973-0"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.2144\/btn-2018-0025"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911031"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11665-0"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jisp.2017.10.014"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.03.008"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.113"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23994"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.563148"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.032"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.001"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18356"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.12.019"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2015.1120930"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.12771234.x"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2008.00739.x"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13904"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806409200"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14300","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/exd.14300","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T11:18:40Z","timestamp":1693567120000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.14300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/exd.14300"],"URL":"https:\/\/doi.org\/10.1111\/exd.14300","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"2020-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}