Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive

Nai Yang Fu; Anne C. Rios; Bhupinder Pal; Charity W. Law; Paul Jamieson; Ruijie Liu; François Vaillant; Felicity Jackling; Kevin He Liu; Gordon K. Smyth; Geoffrey J. Lindeman; Matthew E. Ritchie; Jane E. Visvader

doi:10.1038/ncb3471

Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive

Nai Yang Fu, Anne C. Rios, Bhupinder Pal, Charity W. Law, Paul Jamieson, Ruijie Liu, François Vaillant, Felicity Jackling, Kevin He Liu, Gordon K. Smyth, Geoffrey J. Lindeman, Matthew E. Ritchie, Jane E. Visvader

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5 + basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5 + Tspan8 hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5 + Tspan8 hi cells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.

Originele taal-2	Engels
Pagina's (van-tot)	164-176
Aantal pagina's	13
Tijdschrift	Nature Cell Biology
Volume	19
Nummer van het tijdschrift	3
DOI's	https://doi.org/10.1038/ncb3471
Status	Gepubliceerd - 1 mrt. 2017
Extern gepubliceerd	Ja

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title = "Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive",

abstract = "Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5 + basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5 + Tspan8 hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5 + Tspan8 hi cells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.",

author = "Fu, {Nai Yang} and Rios, {Anne C.} and Bhupinder Pal and Law, {Charity W.} and Paul Jamieson and Ruijie Liu and Fran{\c c}ois Vaillant and Felicity Jackling and Liu, {Kevin He} and Smyth, {Gordon K.} and Lindeman, {Geoffrey J.} and Ritchie, {Matthew E.} and Visvader, {Jane E.}",

note = "Funding Information: We are grateful to the Animal, FACS, Monoclonal Antibody (Bundoora), Imaging and Histology facilities at WEHI and to M. Milevskiy for discussions. This work was supported by the Australian National Health and Medical Research Council (NHMRC) grants no. 1016701, no. 1024852, no. 1054618, no. 1059622, no. 1085191, no. 1086727, no. 1100807;NHMRC IRIISS; the Victorian StateGovernment through Victorian Cancer Agency (VCA) funding and Operational Infrastructure Support; and the Australian Cancer Research Foundation. N.Y.F. and A.C.R. were supported by a National Breast Cancer Foundation (NBCF)/Cure Cancer Australia Fellowship; B.P. by a NHMRC Fellowship no. 1016571 and a VCA Fellowship; G.K.S., G.J.L., M.E.R. and J.E.V. by NHMRC Fellowships no. 1058892, no. 1078730, no. 1104924, no. 1102742.",

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AU - Fu, Nai Yang

AU - Rios, Anne C.

AU - Pal, Bhupinder

AU - Law, Charity W.

AU - Jamieson, Paul

AU - Liu, Ruijie

AU - Vaillant, François

AU - Jackling, Felicity

AU - Liu, Kevin He

AU - Smyth, Gordon K.

AU - Lindeman, Geoffrey J.

AU - Ritchie, Matthew E.

AU - Visvader, Jane E.

N1 - Funding Information: We are grateful to the Animal, FACS, Monoclonal Antibody (Bundoora), Imaging and Histology facilities at WEHI and to M. Milevskiy for discussions. This work was supported by the Australian National Health and Medical Research Council (NHMRC) grants no. 1016701, no. 1024852, no. 1054618, no. 1059622, no. 1085191, no. 1086727, no. 1100807;NHMRC IRIISS; the Victorian StateGovernment through Victorian Cancer Agency (VCA) funding and Operational Infrastructure Support; and the Australian Cancer Research Foundation. N.Y.F. and A.C.R. were supported by a National Breast Cancer Foundation (NBCF)/Cure Cancer Australia Fellowship; B.P. by a NHMRC Fellowship no. 1016571 and a VCA Fellowship; G.K.S., G.J.L., M.E.R. and J.E.V. by NHMRC Fellowships no. 1058892, no. 1078730, no. 1104924, no. 1102742.

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N2 - Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5 + basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5 + Tspan8 hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5 + Tspan8 hi cells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.

AB - Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5 + basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5 + Tspan8 hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5 + Tspan8 hi cells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.

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Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive

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