A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors

Ísberg, Ólöf Gerður; Kim, Jiyoung; Fridriksdottir, Agla; Morsing, Mikkel; Timmermans-Wielenga, Vera; Rønnov-Jessen, Lone; Petersen, Ole W.; Villadsen, René

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dc.contributor	Háskóli Íslands
dc.contributor	University of Iceland
dc.contributor.author	Ísberg, Ólöf Gerður
dc.contributor.author	Kim, Jiyoung
dc.contributor.author	orcid.org/0000-0002-5582-5996 Fridriksdottir, Agla
dc.contributor.author	Morsing, Mikkel
dc.contributor.author	Timmermans-Wielenga, Vera
dc.contributor.author	Rønnov-Jessen, Lone
dc.contributor.author	Petersen, Ole W.
dc.contributor.author	Villadsen, René
dc.date.accessioned	2020-02-12T14:36:40Z
dc.date.available	2020-02-12T14:36:40Z
dc.date.issued	2019-10-16
dc.identifier.citation	Gerdur Ísberg, Ó., Kim, J., Fridriksdottir, A.J. et al. A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors. Scientific Reports 9, 14843 (2019). https://doi.org/10.1038/s41598-019-50903-9
dc.identifier.issn	2045-2322
dc.identifier.uri	https://hdl.handle.net/20.500.11815/1531
dc.description	Publisher's version (útgefin grein).
dc.description.abstract	Human breast cancer is believed to arise in luminal progenitors within the normal breast. A subset of these are double positive (DP) for basal and luminal keratins and localizes to a putative stem cell zone within ducts. We here present a new protocol based on a combination of CD146 with CD117 and CD326 which provides an up to thirty fold enrichment of the DP cells. We show by expression profiling, colony formation, and morphogenesis that CD146high/CD117high/CD326high DP cells belong to a luminal progenitor compartment. While these DP cells are located quite uniformly in ducts, with age a variant type of DP (vDP) cells, which is mainly CD146-negative, accumulates in lobules. Intriguingly, in specimens with BRCA1 mutations known to predispose for cancer, higher frequencies of lobular vDP cells are observed. We propose that vDP cells are strong candidates for tracing the cellular origin of breast cancer.
dc.description.sponsorship	We thank Lena Kristensen, Tove Marianne Lund and Anita Sharma Friismose for expert technical assistance. Benedikte Thuesen and Trine Foged Henriksen, Capio CFR Hospitaler are acknowledged for providing breast biopsy material. The Core Facility for Integrated Microscopy (University of Copenhagen) is acknowledged for confocal microscope accessibility. This work was supported by Novo Nordisk Fonden and Danish Research Council grant 10-092798 (to DanStem), Toyota-Fonden Denmark and Anita og Tage Therkelsens Fond (to R.V.), Familien Erichsens Mindefond and Vera og Carl Johan Michaelsens Legat (to J.K.), Harboefonden, Else og Mogens Wedell-wedellborgs Fond and Danish Cancer Society Grant R146-A9257 (to L.R.-J.).
dc.format.extent	14843
dc.language.iso	en
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartofseries	Scientific Reports;9(1)
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Adult stem cells
dc.subject	Breast cancer
dc.subject	Cell biology
dc.subject	Brjóstakrabbamein
dc.subject	Frumulíffræði
dc.subject	Stofnfrumurannsóknir
dc.subject	Krabbameinsrannsóknir
dc.title	A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors
dc.type	info:eu-repo/semantics/article
dcterms.license	Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.description.version	Peer Reviewed
dc.identifier.journal	Scientific Reports
dc.identifier.doi	10.1038/s41598-019-50903-9
dc.contributor.department	Biomedical Center (UI)
dc.contributor.department	Lífvísindasetur (HÍ)
dc.contributor.school	Heilbrigðisvísindasvið (HÍ)
dc.contributor.school	School of Health Sciences (UI)