{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:47:41Z","timestamp":1792784861229,"version":"4.5.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"FAR 2019"},{"DOI":"10.13039\/501100003407","name":"Ministero dell'Istruzione, dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["CTN01_E48C13000140008"],"award-info":[{"award-number":["CTN01_E48C13000140008"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009879","name":"Regione Emilia-Romagna","doi-asserted-by":"publisher","award":["E92I16000220005"],"award-info":[{"award-number":["E92I16000220005"]}],"id":[{"id":"10.13039\/501100009879","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Debra Alto Adige, Lombardia \u00e8 ricerca"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autologous epidermal cultures restore a functional epidermis on burned patients. Transgenic epidermal grafts do so also in genetic skin diseases such as Junctional Epidermolysis Bullosa. Clinical success strictly requires an adequate number of epidermal stem cells, detected as holoclone-forming cells, which can be only partially distinguished from the other clonogenic keratinocytes and cannot be prospectively isolated. Here we report that single-cell transcriptome analysis of primary human epidermal cultures identifies categories of genes clearly distinguishing the different keratinocyte clonal types, which are hierarchically organized along a continuous, mainly linear trajectory showing that stem cells sequentially generate progenitors producing terminally differentiated cells. Holoclone-forming cells display stem cell hallmarks as genes regulating DNA repair, chromosome segregation, spindle organization and telomerase activity. Finally, we identify\n                    <jats:italic>FOXM1<\/jats:italic>\n                    as a YAP-dependent key regulator of epidermal stem cells. These findings improve criteria for measuring stem cells in epidermal cultures, which is an essential feature of the graft.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-22779-9","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T06:03:29Z","timestamp":1620108209000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Single-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells"],"prefix":"10.1038","volume":"12","author":[{"given":"Elena","family":"Enzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Secone Seconetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-6576","authenticated-orcid":false,"given":"Mattia","family":"Forcato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tenedini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5236-6982","authenticated-orcid":false,"given":"Maria Pia","family":"Polito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Carulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Contin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-3629","authenticated-orcid":false,"given":"Clelia","family":"Peano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Tagliafico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-7078","authenticated-orcid":false,"given":"Silvio","family":"Bicciato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bondanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0850-8445","authenticated-orcid":false,"given":"Michele","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"22779_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/489215a","volume":"489","author":"L De Rosa","year":"2012","unstructured":"De Rosa, L. & De Luca, M. Cell biology: dormant and restless skin stem cells. Nature 489, 215\u2013217 (2012).","journal-title":"Nature"},{"key":"22779_CR2","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nature05574","volume":"446","author":"E Clayton","year":"2007","unstructured":"Clayton, E. et al. A single type of progenitor cell maintains normal epidermis. Nature 446, 185\u2013189 (2007).","journal-title":"Nature"},{"key":"22779_CR3","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/nature11393","volume":"489","author":"G Mascre","year":"2012","unstructured":"Mascre, G. et al. Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature 489, 257\u2013262 (2012).","journal-title":"Nature"},{"key":"22779_CR4","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1073\/pnas.84.8.2302","volume":"84","author":"Y Barrandon","year":"1987","unstructured":"Barrandon, Y. & Green, H. Three clonal types of keratinocyte with different capacities for multiplication. Proc. Natl Acad. Sci. USA 84, 2302\u20132306 (1987).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR5","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nature24487","volume":"551","author":"T Hirsch","year":"2017","unstructured":"Hirsch, T. et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature 551, 327\u2013332 (2017).","journal-title":"Nature"},{"key":"22779_CR6","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1083\/jcb.145.4.769","volume":"145","author":"G Pellegrini","year":"1999","unstructured":"Pellegrini, G. et al. Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J. Cell Biol. 145, 769\u2013782 (1999).","journal-title":"J. Cell Biol."},{"key":"22779_CR7","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/0092-8674(94)90383-2","volume":"76","author":"A Rochat","year":"1994","unstructured":"Rochat, A., Kobayashi, K. & Barrandon, Y. Location of stem cells of human hair follicles by clonal analysis. Cell 76, 1063\u20131073 (1994).","journal-title":"Cell"},{"key":"22779_CR8","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1056\/NEJM198408163110706","volume":"311","author":"GG Gallico","year":"1984","unstructured":"Gallico, G. G. III, O\u2019Connor, N. E., Compton, C. C., Kehinde, O. & Green, H. Permanent coverage of large burn wounds with autologous cultured human epithelium. N. Engl. J. Med 311, 448\u2013451 (1984).","journal-title":"N. Engl. J. Med"},{"key":"22779_CR9","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1056\/NEJMoa0905955","volume":"363","author":"P Rama","year":"2010","unstructured":"Rama, P. et al. Limbal stem-cell therapy and long-term corneal regeneration. N. Engl. J. Med. 363, 147\u2013155 (2010).","journal-title":"N. Engl. J. Med."},{"key":"22779_CR10","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41556-019-0344-z","volume":"21","author":"M De Luca","year":"2019","unstructured":"De Luca, M. et al. Advances in stem cell research and therapeutic development. Nat. Cell Biol. 21, 801\u2013811 (2019).","journal-title":"Nat. Cell Biol."},{"key":"22779_CR11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2217\/17460751.1.1.45","volume":"1","author":"M De Luca","year":"2006","unstructured":"De Luca, M., Pellegrini, G. & Green, H. Regeneration of squamous epithelia from stem cells of cultured grafts. Regen. Med. 1, 45\u201357 (2006).","journal-title":"Regen. Med."},{"key":"22779_CR12","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/19531","volume":"398","author":"AA Mills","year":"1999","unstructured":"Mills, A. A. et al. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398, 708\u2013713 (1999).","journal-title":"Nature"},{"key":"22779_CR13","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.cell.2007.02.045","volume":"129","author":"M Senoo","year":"2007","unstructured":"Senoo, M., Pinto, F., Crum, C. P. & McKeon, F. p63 is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129, 523\u2013536 (2007).","journal-title":"Cell"},{"key":"22779_CR14","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/S1097-2765(00)80275-0","volume":"2","author":"A Yang","year":"1998","unstructured":"Yang, A. et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol. Cell 2, 305\u2013316 (1998).","journal-title":"Mol. Cell"},{"key":"22779_CR15","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/19539","volume":"398","author":"A Yang","year":"1999","unstructured":"Yang, A. et al. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398, 714\u2013718 (1999).","journal-title":"Nature"},{"key":"22779_CR16","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1016\/j.celrep.2019.04.055","volume":"27","author":"L De Rosa","year":"2019","unstructured":"De Rosa, L. et al. Laminin 332-dependent YAP dysregulation depletes epidermal stem cells in junctional epidermolysis bullosa. Cell Rep. 27, 2036\u20132049 e2036 (2019).","journal-title":"Cell Rep."},{"key":"22779_CR17","doi-asserted-by":"publisher","first-page":"6888","DOI":"10.1073\/pnas.87.17.6888","volume":"87","author":"M De Luca","year":"1990","unstructured":"De Luca, M. et al. Polarized integrin mediates human keratinocyte adhesion to basal lamina. Proc. Natl Acad. Sci. USA 87, 6888\u20136892 (1990).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR18","doi-asserted-by":"publisher","first-page":"8970","DOI":"10.1073\/pnas.87.22.8970","volume":"87","author":"MA Stepp","year":"1990","unstructured":"Stepp, M. A., Spurr-Michaud, S., Tisdale, A., Elwell, J. & Gipson, I. K. Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes. Proc. Natl Acad. Sci. USA 87, 8970\u20138974 (1990).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR19","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/0092-8674(93)90251-K","volume":"73","author":"PH Jones","year":"1993","unstructured":"Jones, P. H. & Watt, F. M. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 73, 713\u2013724 (1993).","journal-title":"Cell"},{"key":"22779_CR20","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1073\/pnas.061032098","volume":"98","author":"G Pellegrini","year":"2001","unstructured":"Pellegrini, G. et al. p63 identifies keratinocyte stem cells. Proc. Natl Acad. Sci. USA 98, 3156\u20133161 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14744","volume":"8","author":"G Walko","year":"2017","unstructured":"Walko, G. et al. A genome-wide screen identifies YAP\/WBP2 interplay conferring growth advantage on human epidermal stem cells. Nat. Commun. 8, 14744 (2017).","journal-title":"Nat. Commun."},{"key":"22779_CR22","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1083\/jcb.149.5.1117","volume":"149","author":"E Dellambra","year":"2000","unstructured":"Dellambra, E. et al. Downregulation of 14-3-3sigma prevents clonal evolution and leads to immortalization of primary human keratinocytes. J. Cell Biol. 149, 1117\u20131130 (2000).","journal-title":"J. Cell Biol."},{"key":"22779_CR23","doi-asserted-by":"publisher","first-page":"10371","DOI":"10.1073\/pnas.93.19.10371","volume":"93","author":"MB Mathor","year":"1996","unstructured":"Mathor, M. B. et al. Clonal analysis of stably transduced human epidermal stem cells in culture. Proc. Natl Acad. Sci. USA 93, 10371\u201310376 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-018-0266-6","volume":"16","author":"GB Liao","year":"2018","unstructured":"Liao, G. B. et al. Regulation of the master regulator FOXM1 in cancer. Cell Commun. Signal 16, 57 (2018).","journal-title":"Cell Commun. Signal"},{"key":"22779_CR25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/B978-0-12-407190-2.00016-2","volume":"119","author":"I Wierstra","year":"2013","unstructured":"Wierstra, I. FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy. Adv. Cancer Res. 119, 191\u2013419 (2013).","journal-title":"Adv. Cancer Res."},{"key":"22779_CR26","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.scr.2016.03.007","volume":"16","author":"CT Kwok","year":"2016","unstructured":"Kwok, C. T. et al. The Forkhead box transcription factor FOXM1 is required for the maintenance of cell proliferation and protection against oxidative stress in human embryonic stem cells. Stem Cell Res. 16, 651\u2013661 (2016).","journal-title":"Stem Cell Res"},{"key":"22779_CR27","doi-asserted-by":"publisher","first-page":"8027","DOI":"10.1093\/nar\/gkq715","volume":"38","author":"Z Xie","year":"2010","unstructured":"Xie, Z. et al. Foxm1 transcription factor is required for maintenance of pluripotency of P19 embryonal carcinoma cells. Nucleic Acids Res. 38, 8027\u20138038 (2010).","journal-title":"Nucleic Acids Res."},{"key":"22779_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21876-y","volume":"8","author":"ZM Besharat","year":"2018","unstructured":"Besharat, Z. M. et al. Foxm1 controls a pro-stemness microRNA network in neural stem cells. Sci. Rep. 8, 3523 (2018).","journal-title":"Sci. Rep."},{"key":"22779_CR29","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/ni.3204","volume":"16","author":"Y Hou","year":"2015","unstructured":"Hou, Y. et al. The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells. Nat. Immunol. 16, 810\u2013818 (2015).","journal-title":"Nat. Immunol."},{"key":"22779_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2375-6","volume":"11","author":"Z Chen","year":"2020","unstructured":"Chen, Z. et al. A Cdh1-FoxM1-Apc axis controls muscle development and regeneration. Cell Death Dis. 11, 180 (2020).","journal-title":"Cell Death Dis."},{"key":"22779_CR31","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ydbio.2012.07.028","volume":"370","author":"V Ustiyan","year":"2012","unstructured":"Ustiyan, V. et al. Foxm1 transcription factor is critical for proliferation and differentiation of Clara cells during development of conducting airways. Dev. Biol. 370, 198\u2013212 (2012).","journal-title":"Dev. Biol."},{"key":"22779_CR32","doi-asserted-by":"publisher","first-page":"4527","DOI":"10.1093\/nar\/gkq194","volume":"38","author":"DR Littler","year":"2010","unstructured":"Littler, D. R. et al. Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence. Nucleic Acids Res. 38, 4527\u20134538 (2010).","journal-title":"Nucleic Acids Res"},{"key":"22779_CR33","first-page":"11","volume":"3","author":"AK Lam","year":"2013","unstructured":"Lam, A. K. et al. FOXM1b, which is present at elevated levels in cancer cells, has a greater transforming potential than FOXM1c. Front. Oncol. 3, 11 (2013).","journal-title":"Front. Oncol."},{"key":"22779_CR34","doi-asserted-by":"publisher","first-page":"E3402","DOI":"10.1073\/pnas.1420005112","volume":"112","author":"TS Eisinger-Mathason","year":"2015","unstructured":"Eisinger-Mathason, T. S. et al. Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis. Proc. Natl Acad. Sci. USA 112, E3402\u20133411 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR35","doi-asserted-by":"publisher","first-page":"5117","DOI":"10.1038\/onc.2012.5","volume":"31","author":"T Mizuno","year":"2012","unstructured":"Mizuno, T. et al. YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle-promoting genes. Oncogene 31, 5117\u20135122 (2012).","journal-title":"Oncogene"},{"key":"22779_CR36","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","volume":"70","author":"JD Fine","year":"2014","unstructured":"Fine, J. D. et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J. Am. Acad. Dermatol. 70, 1103\u20131126 (2014).","journal-title":"J. Am. Acad. Dermatol"},{"key":"22779_CR37","doi-asserted-by":"publisher","first-page":"5665","DOI":"10.1073\/pnas.76.11.5665","volume":"76","author":"H Green","year":"1979","unstructured":"Green, H., Kehinde, O. & Thomas, J. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc. Natl Acad. Sci. USA 76, 5665\u20135668 (1979).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR38","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1038\/nm1504","volume":"12","author":"F Mavilio","year":"2006","unstructured":"Mavilio, F. et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat. Med. 12, 1397\u20131402 (2006).","journal-title":"Nat. Med."},{"key":"22779_CR39","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1097\/00007890-199909270-00021","volume":"68","author":"G Pellegrini","year":"1999","unstructured":"Pellegrini, G. et al. The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin. Transplantation 68, 868\u2013879 (1999).","journal-title":"Transplantation"},{"key":"22779_CR40","doi-asserted-by":"publisher","first-page":"9523","DOI":"10.1073\/pnas.0503437102","volume":"102","author":"E Di Iorio","year":"2005","unstructured":"Di Iorio, E. et al. Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Proc. Natl Acad. Sci. USA 102, 9523\u20139528 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR41","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nrm2848","volume":"11","author":"RJ O\u2019Sullivan","year":"2010","unstructured":"O\u2019Sullivan, R. J. & Karlseder, J. Telomeres: protecting chromosomes against genome instability. Nat. Rev. Mol. Cell Biol. 11, 171\u2013181 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"22779_CR42","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ceb.2006.12.012","volume":"19","author":"R Basu","year":"2007","unstructured":"Basu, R. & Chang, F. Shaping the actin cytoskeleton using microtubule tips. Curr. Opin. Cell Biol. 19, 88\u201394 (2007).","journal-title":"Curr. Opin. Cell Biol."},{"key":"22779_CR43","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41580-018-0067-1","volume":"20","author":"M Dogterom","year":"2019","unstructured":"Dogterom, M. & Koenderink, G. H. Actin-microtubule crosstalk in cell biology. Nat. Rev. Mol. Cell Biol. 20, 38\u201354 (2019).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"22779_CR44","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1002\/emmm.201201839","volume":"5","author":"D Nanba","year":"2013","unstructured":"Nanba, D. et al. Actin filament dynamics impacts keratinocyte stem cell maintenance. EMBO Mol. Med. 5, 640\u2013653 (2013).","journal-title":"EMBO Mol. Med."},{"key":"22779_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18075-7","volume":"11","author":"S Wang","year":"2020","unstructured":"Wang, S. et al. Single cell transcriptomics of human epidermis identifies basal stem cell transition states. Nat. Commun. 11, 4239 (2020).","journal-title":"Nat. Commun."},{"key":"22779_CR46","doi-asserted-by":"publisher","unstructured":"De Rosa, L. et al. Toward combined cell and gene therapy for genodermatoses. Cold Spring Harb. Perspect. Biol. 12, https:\/\/doi.org\/10.1101\/cshperspect.a035667 (2020).","DOI":"10.1101\/cshperspect.a035667"},{"key":"22779_CR47","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41586-020-2555-7","volume":"584","author":"M Aragona","year":"2020","unstructured":"Aragona, M. et al. Mechanisms of stretch-mediated skin expansion at single-cell resolution. Nature 584, 268\u2013273 (2020).","journal-title":"Nature"},{"key":"22779_CR48","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.cell.2020.03.015","volume":"181","author":"S Dekoninck","year":"2020","unstructured":"Dekoninck, S. et al. Defining the design principles of skin epidermis postnatal growth. Cell 181, 604\u2013620 e622 (2020).","journal-title":"Cell"},{"key":"22779_CR49","doi-asserted-by":"publisher","first-page":"42792","DOI":"10.18632\/oncotarget.8669","volume":"7","author":"FC Kelleher","year":"2016","unstructured":"Kelleher, F. C. & O\u2019Sullivan, H. FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways. Oncotarget 7, 42792\u201342804 (2016).","journal-title":"Oncotarget"},{"key":"22779_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1384-y","volume":"19","author":"A Ghahramani","year":"2018","unstructured":"Ghahramani, A., Donati, G., Luscombe, N. M. & Watt, F. M. Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells. Genome Biol. 19, 3 (2018).","journal-title":"Genome Biol."},{"key":"22779_CR51","doi-asserted-by":"publisher","unstructured":"Solberg, N. T., Melheim, M., Strand, M. F., Olsen, P. A. & Krauss, S. MEK inhibition induces canonical WNT signaling through YAP in KRAS mutated HCT-15 cells, and a cancer preventive FOXO3\/FOXM1 ratio in combination with TNKS inhibition. Cancers (Basel) 11, https:\/\/doi.org\/10.3390\/cancers11020164 (2019).","DOI":"10.3390\/cancers11020164"},{"key":"22779_CR52","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1053\/j.gastro.2017.02.018","volume":"152","author":"SME Weiler","year":"2017","unstructured":"Weiler, S. M. E. et al. Induction of chromosome instability by activation of Yes-associated protein and Forkhead Box M1 in liver cancer. Gastroenterology 152, 2037\u20132051 e2022 (2017).","journal-title":"Gastroenterology"},{"key":"22779_CR53","doi-asserted-by":"publisher","first-page":"4684","DOI":"10.3390\/ijms14034684","volume":"14","author":"F Bisson","year":"2013","unstructured":"Bisson, F. et al. Irradiated human dermal fibroblasts are as efficient as mouse fibroblasts as a feeder layer to improve human epidermal cell culture lifespan. Int J. Mol. Sci. 14, 4684\u20134704 (2013).","journal-title":"Int J. Mol. Sci."},{"key":"22779_CR54","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","volume":"4","author":"RA Irizarry","year":"2003","unstructured":"Irizarry, R. A. et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4, 249\u2013264 (2003).","journal-title":"Biostatistics"},{"key":"22779_CR55","doi-asserted-by":"publisher","first-page":"e175","DOI":"10.1093\/nar\/gni179","volume":"33","author":"M Dai","year":"2005","unstructured":"Dai, M. et al. Evolving gene\/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 33, e175 (2005).","journal-title":"Nucleic Acids Res."},{"key":"22779_CR56","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.1073\/pnas.091062498","volume":"98","author":"VG Tusher","year":"2001","unstructured":"Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl Acad. Sci. USA 98, 5116\u20135121 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR57","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"W Huang da","year":"2009","unstructured":"Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44\u201357 (2009).","journal-title":"Nat. Protoc."},{"key":"22779_CR58","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22779_CR59","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417\u2013425 (2015).","journal-title":"Cell Syst."},{"key":"22779_CR60","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.15252\/embj.201490379","volume":"34","author":"E Enzo","year":"2015","unstructured":"Enzo, E. et al. Aerobic glycolysis tunes YAP\/TAZ transcriptional activity. EMBO J. 34, 1349\u20131370 (2015).","journal-title":"EMBO J."},{"key":"22779_CR61","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902 e1821 (2019).","journal-title":"Cell"},{"key":"22779_CR62","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496\u2013502 (2019).","journal-title":"Nature"},{"key":"22779_CR63","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/S0042-6822(88)90101-8","volume":"167","author":"D Markowitz","year":"1988","unstructured":"Markowitz, D., Goff, S. & Bank, A. Construction and use of a safe and efficient amphotropic packaging cell line. Virology 167, 400\u2013406 (1988).","journal-title":"Virology"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22779-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22779-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22779-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T06:53:54Z","timestamp":1669964034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22779-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["22779"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-22779-9","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"assertion":[{"value":"4 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.D.L. is co-founder and member of the Board of Directors of Holostem Terapie Avanzate (HTA), s.r.l, Modena, Italy, as well as consultants for J-TEC-Japan Tissue Engineering, Ltd. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2505"}}