In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation

Bethan Lloyd-Lewis; Francesca  Gobbo; Meghan  Perkins; Guillaume Jacquemin; Mathilde Huyghe; Marisa Faraldo; Silvia Fre

doi:10.1016/j.celrep.2022.110461

In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation

Bethan Lloyd-Lewis, Francesca Gobbo, Meghan Perkins, Guillaume Jacquemin, Mathilde Huyghe, Marisa Faraldo, Silvia Fre^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

9 Citations (Scopus)

137 Downloads (Pure)

Abstract

Real-time in vivo imaging provides an essential window into the spatiotemporal cellular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we capture the earliest cellular events arising in response to active Wnt/β-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either the mammary luminal or basal epithelial lineage, leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo and reveal that, in mammary neoplastic development, β-catenin activation dictates a hair follicle/epidermal differentiation program independently of the targeted cell of origin.

Original language	English
Article number	110461
Number of pages	20
Journal	Cell Reports
Volume	38
Issue number	10
DOIs	https://doi.org/10.1016/j.celrep.2022.110461
Publication status	Published - 8 Mar 2022

Bibliographical note

Funding Information:
The authors thank P. Chambon and D. Metzger for providing the SMACre ERT2 (Acta2-Cre ERT2 ) mice, S. Tajbakhsh for the R26 mTmG reporter line, and L. Larue for sharing the Catnb +/lox(ex3) line. We acknowledge the flow cytometry and cell sorting platform at Institute Curie for their expertise, the in vivo experimental facility for help in the maintenance and care of our mouse colony, and the experimental pathology facility at Curie Hospital for paraffin sample preparation. The authors especially thank L. Sengmanivong and M. Irondelle for intravital imaging support and C. Carabaña for technical assistance with in vivo experiments. The PICT-IBiSA imaging platform was funded by ANR-10-INBS-04 (France-BioImaging), ANR-11 BSV2 012 01, ERC ZEBRATECTUM no. 311159, ARC SFI20121205686, and the Schlumberger Foundation. This work was supported by PSL ∗ Research University , French National Research Agency (ANR) ( ANR-15-CE13-0013-01 ), FRM Equipes ( EQU201903007821 ), FSER (Schlumberger Foundation) ( FSER20200211117 ), and Labex DEEP (ANR- 11-LBX-0044 ). B.L.-L. is also funded by a Vice-Chancellor's Research Fellowship from the University of Bristol and acknowledges support from the Academy of Medical Sciences / Wellcome Trust / the Government Department of Business , Energy and Industrial Strategy / British Heart Foundation / Diabetes UK Springboard Award [ SBF003/1170 ], Elizabeth Blackwell Institute for Health Research ( University of Bristol ), and Wellcome Trust Institutional Strategic Support Fund ( 204813/Z/16/Z ).

Publisher Copyright:
© 2022 The Author(s)

Keywords

mammary gland development
lineage tracing
β-catenin
Wnt signaling
intravital imaging
in vivo imaging

Access to Document

10.1016/j.celrep.2022.110461Licence: Unspecified

Full-text PDF (final published version)
This is the final published version of the article (version of record). It first appeared online via Cell Press at https://doi.org/10.1016/j.celrep.2022.110461. Please refer to any applicable terms of use of the publisher.
Final published version, 5.74 MBLicence: CC BY

Handle.net

Persistent link

Cite this

@article{50118c49220c49a7b1697eab9aa675d0,

title = "In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation",

abstract = "Real-time in vivo imaging provides an essential window into the spatiotemporal cellular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we capture the earliest cellular events arising in response to active Wnt/β-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either the mammary luminal or basal epithelial lineage, leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo and reveal that, in mammary neoplastic development, β-catenin activation dictates a hair follicle/epidermal differentiation program independently of the targeted cell of origin.",

keywords = "mammary gland development, lineage tracing, β-catenin, Wnt signaling, intravital imaging, in vivo imaging",

author = "Bethan Lloyd-Lewis and Francesca Gobbo and Meghan Perkins and Guillaume Jacquemin and Mathilde Huyghe and Marisa Faraldo and Silvia Fre",

note = "Funding Information: The authors thank P. Chambon and D. Metzger for providing the SMACre ERT2 (Acta2-Cre ERT2 ) mice, S. Tajbakhsh for the R26 mTmG reporter line, and L. Larue for sharing the Catnb +/lox(ex3) line. We acknowledge the flow cytometry and cell sorting platform at Institute Curie for their expertise, the in vivo experimental facility for help in the maintenance and care of our mouse colony, and the experimental pathology facility at Curie Hospital for paraffin sample preparation. The authors especially thank L. Sengmanivong and M. Irondelle for intravital imaging support and C. Caraba{\~n}a for technical assistance with in vivo experiments. The PICT-IBiSA imaging platform was funded by ANR-10-INBS-04 (France-BioImaging), ANR-11 BSV2 012 01, ERC ZEBRATECTUM no. 311159, ARC SFI20121205686, and the Schlumberger Foundation. This work was supported by PSL ∗ Research University , French National Research Agency (ANR) ( ANR-15-CE13-0013-01 ), FRM Equipes ( EQU201903007821 ), FSER (Schlumberger Foundation) ( FSER20200211117 ), and Labex DEEP (ANR- 11-LBX-0044 ). B.L.-L. is also funded by a Vice-Chancellor's Research Fellowship from the University of Bristol and acknowledges support from the Academy of Medical Sciences / Wellcome Trust / the Government Department of Business , Energy and Industrial Strategy / British Heart Foundation / Diabetes UK Springboard Award [ SBF003/1170 ], Elizabeth Blackwell Institute for Health Research ( University of Bristol ), and Wellcome Trust Institutional Strategic Support Fund ( 204813/Z/16/Z ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = mar,

day = "8",

doi = "10.1016/j.celrep.2022.110461",

language = "English",

volume = "38",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "10",

}

TY - JOUR

T1 - In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation

AU - Lloyd-Lewis, Bethan

AU - Gobbo, Francesca

AU - Perkins, Meghan

AU - Jacquemin, Guillaume

AU - Huyghe, Mathilde

AU - Faraldo, Marisa

AU - Fre, Silvia

N1 - Funding Information: The authors thank P. Chambon and D. Metzger for providing the SMACre ERT2 (Acta2-Cre ERT2 ) mice, S. Tajbakhsh for the R26 mTmG reporter line, and L. Larue for sharing the Catnb +/lox(ex3) line. We acknowledge the flow cytometry and cell sorting platform at Institute Curie for their expertise, the in vivo experimental facility for help in the maintenance and care of our mouse colony, and the experimental pathology facility at Curie Hospital for paraffin sample preparation. The authors especially thank L. Sengmanivong and M. Irondelle for intravital imaging support and C. Carabaña for technical assistance with in vivo experiments. The PICT-IBiSA imaging platform was funded by ANR-10-INBS-04 (France-BioImaging), ANR-11 BSV2 012 01, ERC ZEBRATECTUM no. 311159, ARC SFI20121205686, and the Schlumberger Foundation. This work was supported by PSL ∗ Research University , French National Research Agency (ANR) ( ANR-15-CE13-0013-01 ), FRM Equipes ( EQU201903007821 ), FSER (Schlumberger Foundation) ( FSER20200211117 ), and Labex DEEP (ANR- 11-LBX-0044 ). B.L.-L. is also funded by a Vice-Chancellor's Research Fellowship from the University of Bristol and acknowledges support from the Academy of Medical Sciences / Wellcome Trust / the Government Department of Business , Energy and Industrial Strategy / British Heart Foundation / Diabetes UK Springboard Award [ SBF003/1170 ], Elizabeth Blackwell Institute for Health Research ( University of Bristol ), and Wellcome Trust Institutional Strategic Support Fund ( 204813/Z/16/Z ). Publisher Copyright: © 2022 The Author(s)

PY - 2022/3/8

Y1 - 2022/3/8

N2 - Real-time in vivo imaging provides an essential window into the spatiotemporal cellular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we capture the earliest cellular events arising in response to active Wnt/β-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either the mammary luminal or basal epithelial lineage, leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo and reveal that, in mammary neoplastic development, β-catenin activation dictates a hair follicle/epidermal differentiation program independently of the targeted cell of origin.

AB - Real-time in vivo imaging provides an essential window into the spatiotemporal cellular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we capture the earliest cellular events arising in response to active Wnt/β-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either the mammary luminal or basal epithelial lineage, leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo and reveal that, in mammary neoplastic development, β-catenin activation dictates a hair follicle/epidermal differentiation program independently of the targeted cell of origin.

KW - mammary gland development

KW - lineage tracing

KW - β-catenin

KW - Wnt signaling

KW - intravital imaging

KW - in vivo imaging

U2 - 10.1016/j.celrep.2022.110461

DO - 10.1016/j.celrep.2022.110461

M3 - Article (Academic Journal)

C2 - 35263603

SN - 2211-1247

VL - 38

JO - Cell Reports

JF - Cell Reports

IS - 10

M1 - 110461

ER -

In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation

Abstract

Bibliographical note

Keywords

Access to Document

Handle.net

Fingerprint

Cite this