IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28937-x.html
   My bibliography  Save this article

Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency

Author

Listed:
  • Elena Spina

    (New York University School of Medicine)

  • Julia Simundza

    (New York University School of Medicine)

  • Angela Incassati

    (New York University School of Medicine)

  • Anupama Chandramouli

    (New York University School of Medicine
    New York University School of Medicine)

  • Matthias C. Kugler

    (New York University School of Medicine)

  • Ziyan Lin

    (New York University School of Medicine)

  • Alireza Khodadadi-Jamayran

    (New York University School of Medicine)

  • Christine J. Watson

    (University of Cambridge)

  • Pamela Cowin

    (New York University School of Medicine
    New York University School of Medicine)

Abstract

Gpr125 is an orphan G-protein coupled receptor, with homology to cell adhesion and axonal guidance factors, that is implicated in planar polarity and control of cell movements. By lineage tracing we demonstrate that Gpr125 is a highly specific marker of bipotent mammary stem cells in the embryo and of multiple long-lived unipotent basal mammary progenitors in perinatal and postnatal glands. Nipple-proximal Gpr125+ cells express a transcriptomic profile indicative of chemo-repulsion and cell movement, whereas Gpr125+ cells concentrated at invasive ductal tips display a hybrid epithelial-mesenchymal phenotype and are equipped to bind chemokine and growth factors and secrete a promigratory matrix. Gpr125 progenitors acquire bipotency in the context of transplantation and cancer and are greatly expanded and massed at the pushing margins of short latency MMTV-Wnt1 tumors. High Gpr125 expression identifies patients with particularly poor outcome within the basal breast cancer subtype highlighting its potential utility as a factor to stratify risk.

Suggested Citation

  • Elena Spina & Julia Simundza & Angela Incassati & Anupama Chandramouli & Matthias C. Kugler & Ziyan Lin & Alireza Khodadadi-Jamayran & Christine J. Watson & Pamela Cowin, 2022. "Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28937-x
    DOI: 10.1038/s41467-022-28937-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28937-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28937-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Marco Seandel & Daylon James & Sergey V. Shmelkov & Ilaria Falciatori & Jiyeon Kim & Sai Chavala & Douglas S. Scherr & Fan Zhang & Richard Torres & Nicholas W. Gale & George D. Yancopoulos & Andrew Mu, 2007. "Generation of functional multipotent adult stem cells from GPR125+ germline progenitors," Nature, Nature, vol. 449(7160), pages 346-350, September.
    2. Daisong Wang & Cheguo Cai & Xiaobing Dong & Qing Cissy Yu & Xiao-Ou Zhang & Li Yang & Yi Arial Zeng, 2015. "Identification of multipotent mammary stem cells by protein C receptor expression," Nature, Nature, vol. 517(7532), pages 81-84, January.
    3. Felicity M. Davis & Bethan Lloyd-Lewis & Olivia B. Harris & Sarah Kozar & Douglas J. Winton & Leila Muresan & Christine J. Watson, 2016. "Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    4. Bhupinder Pal & Yunshun Chen & François Vaillant & Paul Jamieson & Lavinia Gordon & Anne C. Rios & Stephen Wilcox & Naiyang Fu & Kevin He Liu & Felicity C. Jackling & Melissa J. Davis & Geoffrey J. Li, 2017. "Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    5. Alexandra Van Keymeulen & Ana Sofia Rocha & Marielle Ousset & Benjamin Beck & Gaëlle Bouvencourt & Jason Rock & Neha Sharma & Sophie Dekoninck & Cédric Blanpain, 2011. "Distinct stem cells contribute to mammary gland development and maintenance," Nature, Nature, vol. 479(7372), pages 189-193, November.
    6. Mark Shackleton & François Vaillant & Kaylene J. Simpson & John Stingl & Gordon K. Smyth & Marie-Liesse Asselin-Labat & Li Wu & Geoffrey J. Lindeman & Jane E. Visvader, 2006. "Generation of a functional mammary gland from a single stem cell," Nature, Nature, vol. 439(7072), pages 84-88, January.
    7. Qi Miao & Matthew C. Hill & Fengju Chen & Qianxing Mo & Amy T. Ku & Carlos Ramos & Elisabeth Sock & Véronique Lefebvre & Hoang Nguyen, 2019. "SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
    8. Karsten Bach & Sara Pensa & Marta Grzelak & James Hadfield & David J. Adams & John C. Marioni & Walid T. Khaled, 2017. "Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    9. Balázs Győrffy & Pawel Surowiak & Jan Budczies & András Lánczky, 2013. "Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-8, December.
    10. Anne C. Rios & Nai Yang Fu & Geoffrey J. Lindeman & Jane E. Visvader, 2014. "In situ identification of bipotent stem cells in the mammary gland," Nature, Nature, vol. 506(7488), pages 322-327, February.
    11. Karsten Bach & Sara Pensa & Marija Zarocsinceva & Katarzyna Kania & Julie Stockis & Silvain Pinaud & Kyren A. Lazarus & Mona Shehata & Bruno M. Simões & Alice R. Greenhalgh & Sacha J. Howell & Robert , 2021. "Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ana Sofia Rocha & Alejandro Collado-Solé & Osvaldo Graña-Castro & Jaime Redondo-Pedraza & Gonzalo Soria-Alcaide & Alex Cordero & Patricia G. Santamaría & Eva González-Suárez, 2023. "Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Maša Alečković & Simona Cristea & Carlos R. Gil Del Alcazar & Pengze Yan & Lina Ding & Ethan D. Krop & Nicholas W. Harper & Ernesto Rojas Jimenez & Donghao Lu & Anushree C. Gulvady & Pierre Foidart & , 2022. "Breast cancer prevention by short-term inhibition of TGFβ signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Maryam Ghaderi Najafabadi & G. Kenneth Gray & Li Ren Kong & Komal Gupta & David Perera & Huw Naylor & Joan S. Brugge & Ashok R. Venkitaraman & Mona Shehata, 2023. "A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Zhengcheng He & Ryan Ghorayeb & Susanna Tan & Ke Chen & Amanda C. Lorentzian & Jack Bottyan & Syed Mohammed Musheer Aalam & Miguel Angel Pujana & Philipp F. Lange & Nagarajan Kannan & Connie J. Eaves , 2022. "Pathogenic BRCA1 variants disrupt PLK1-regulation of mitotic spindle orientation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Xing Yang & Haibo Xu & Xu Yang & Hui Wang & Li Zou & Qin Yang & Xiaopeng Qi & Li Li & Hongxia Duan & Xiyun Yan & Nai Yang Fu & Jing Tan & Zongliu Hou & Baowei Jiao, 2024. "Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Ingrid Paine & Arnaud Chauviere & John Landua & Amulya Sreekumar & Vittorio Cristini & Jeffrey Rosen & Michael T Lewis, 2016. "A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud," PLOS Computational Biology, Public Library of Science, vol. 12(4), pages 1-23, April.
    7. Huiru Bai & Xiaoqin Liu & Meizhen Lin & Yuan Meng & Ruolan Tang & Yajing Guo & Nan Li & Michael F. Clarke & Shang Cai, 2024. "Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Alecia-Jane Twigger & Lisa K. Engelbrecht & Karsten Bach & Isabel Schultz-Pernice & Sara Pensa & Jack Stenning & Stefania Petricca & Christina H. Scheel & Walid T. Khaled, 2022. "Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Jiang-jiang Li & Tiantian Yu & Peiting Zeng & Jingyu Tian & Panpan Liu & Shuang Qiao & Shijun Wen & Yumin Hu & Qiao Liu & Wenhua Lu & Hui Zhang & Peng Huang, 2024. "Wild-type IDH2 is a therapeutic target for triple-negative breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Joseph G. Kern & Andrew M. Tilston-Lunel & Anthony Federico & Boting Ning & Amy Mueller & Grace B. Peppler & Eleni Stampouloglou & Nan Cheng & Randy L. Johnson & Marc E. Lenburg & Jennifer E. Beane & , 2022. "Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Paul A Stewart & Katja Parapatics & Eric A Welsh & André C Müller & Haoyun Cao & Bin Fang & John M Koomen & Steven A Eschrich & Keiryn L Bennett & Eric B Haura, 2015. "A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-18, November.
    12. Yongyao Fu & Abigail Pajulas & Jocelyn Wang & Baohua Zhou & Anthony Cannon & Cherry Cheuk Lam Cheung & Jilu Zhang & Huaxin Zhou & Amanda Jo Fisher & David T. Omstead & Sabrina Khan & Lei Han & Jean-Ch, 2022. "Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Toshiyuki Fujita & Naoya Aoki & Chihiro Mori & Koichi J. Homma & Shinji Yamaguchi, 2024. "SoxC and MmpReg promote blastema formation in whole-body regeneration of fragmenting potworms Enchytraeus japonensis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Clare A. Rebbeck & Jian Xian & Susanne Bornelöv & Joseph Geradts & Amy Hobeika & Heather Geiger & Jose Franco Alvarez & Elena Rozhkova & Ashley Nicholls & Nicolas Robine & Herbert K. Lyerly & Gregory , 2022. "Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. Naser Ansari-Pour & Yonglan Zheng & Toshio F. Yoshimatsu & Ayodele Sanni & Mustapha Ajani & Jean-Baptiste Reynier & Avraam Tapinos & Jason J. Pitt & Stefan Dentro & Anna Woodard & Padma Sheila Rajagop, 2021. "Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    16. Amos C. Lee & Yongju Lee & Ahyoun Choi & Han-Byoel Lee & Kyoungseob Shin & Hyunho Lee & Ji Young Kim & Han Suk Ryu & Hoe Suk Kim & Seung Yeon Ryu & Sangeun Lee & Jong-Ho Cheun & Duck Kyun Yoo & Sumin , 2022. "Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    17. Andrew K. Beppu & Juanjuan Zhao & Changfu Yao & Gianni Carraro & Edo Israely & Anna Lucia Coelho & Katherine Drake & Cory M. Hogaboam & William C. Parks & Jay K. Kolls & Barry R. Stripp, 2023. "Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Zhen Lu & Jinyun Chen & Pengfei Yu & Matthew J. Atherton & Jun Gui & Vivek S. Tomar & Justin D. Middleton & Neil T. Sullivan & Sunil Singhal & Subin S. George & Ashley G. Woolfork & Aalim M. Weljie & , 2022. "Tumor factors stimulate lysosomal degradation of tumor antigens and undermine their cross-presentation in lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    19. Ming Yi & Ruoqing Zhu & Robert M Stephens, 2018. "GradientScanSurv—An exhaustive association test method for gene expression data with censored survival outcome," PLOS ONE, Public Library of Science, vol. 13(12), pages 1-28, December.
    20. Bo Yuan & Jingyuan Xiong & Chaoxiong Zhang & Yuqin Yao & Chaoxiong Zhang & Ting An & Jie Liu, 2020. "Prognostic Roles of APLNR Expression in Non-Small Cell Lung Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 27(5), pages 21089-21098, May.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28937-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.