Heterotypic cell–cell communication regulates glandular stem cell multipotency

Centonze, Alessia; Lin, Shuheng; Tika, Elisavet; Sifrim, Alejandro; Fioramonti, Marco; Malfait, Milan; Song, Yura; Wuidart, Aline; Herck, Jens Van; Dannau, Anne; Bouvencourt, Gaëlle; Dubois, Christine; Dedoncker, Nina; Sahay, Amar; Maertelaer, Viviane De; Siebel, Christian Cw; Keymeulen, Alexandra Van; Voet, Thierry; Blanpain, Cédric

doi:10.1038/s41586-020-2632-y

Cited by 102 publications

(93 citation statements)

References 69 publications

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“…Further, either stimulating the TNF pathway or blocking Notch, Wnt and epidermal growth factor receptor (EGFR) signalling inhibits BC multipotency, which could be induced by LC ablation. 44 Together, these results support the notion that signalling communication between the glandular cells is critical to maintaining their lineage identity and restriction to mammary gland stem cells. Interestingly, a comparison of the wound repair processes following LC-specific ablation in four different glands-mammary gland, sweat gland, salivary gland and prostate gland-showed that, in general, unipotent progenitor cells within one lineage, for example LC, respond with the most significant improvement of proliferation rate.…”

Section: Mammary Glandsupporting

confidence: 71%

“…It has been suggested, based on prediction of ligand‐receptor pairs from single‐cell data, that TNF secreted by LCs in the mammary gland may restrict multipotency under normal conditions; therefore, it is likely that when nearby LCs are injured or ablated, loss of TNF may allow BC activation. Further, either stimulating the TNF pathway or blocking Notch, Wnt and epidermal growth factor receptor (EGFR) signalling inhibits BC multipotency, which could be induced by LC ablation 44 . Together, these results support the notion that signalling communication between the glandular cells is critical to maintaining their lineage identity and restriction to mammary gland stem cells.…”

Section: Glandular Wound Repairmentioning

confidence: 57%

“…In contrast to the strict unipotency in sweat gland, mammary gland BCs replenish LCs upon LC-specific injury, via a BC-LC hybrid state. 44 It has been suggested, based on prediction of ligand-receptor pairs from single-cell data, that TNF secreted by LCs in the mammary gland may restrict multipotency under normal conditions; therefore, it is likely that when nearby LCs are injured or ablated, loss of TNF may allow BC activation. Further, either stimulating the TNF pathway or blocking Notch, Wnt and epidermal growth factor receptor (EGFR) signalling inhibits BC multipotency, which could be induced by LC ablation.…”

Section: Mammary Glandmentioning

confidence: 99%

“…Interestingly, a comparison of the wound repair processes following LC‐specific ablation in four different glands—mammary gland, sweat gland, salivary gland and prostate gland—showed that, in general, unipotent progenitor cells within one lineage, for example LC, respond with the most significant improvement of proliferation rate 44 . Moreover, the proliferation rate was minimal in sweat gland compared to mammary gland, indicating that these two types of glands have different degrees of plasticity upon injury induction.…”

Section: Glandular Wound Repairmentioning

confidence: 99%

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Glandular stem cells in the skin during development, homeostasis, wound repair and regeneration

Lin

2021

Experimental Dermatology

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Glands in the skin are essential for various physiological functions involving exocrine secretion. Like other tissues and organs, they possess the ability to repair injury and self-renew during homeostasis. Progenitor cells in glands are mostly unipotent but include some multipotent stem cells that function when extensive remodelling or regeneration is required. In this review, using two glandular models in skin, mouse sweat gland and mammary gland, we discuss lineage restriction that develops during glandular morphogenesis, as well as the mechanisms regulating cell fate and plasticity during wound repair and regeneration. Understanding the intrinsic and extrinsic factors that control the behaviours of glandular stem cell and maintain glandular functions will provide insight into future prospects for glandular regeneration.

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Section: Mammary Glandsupporting

confidence: 71%

Section: Glandular Wound Repairmentioning

confidence: 57%

Section: Mammary Glandmentioning

confidence: 99%

Section: Glandular Wound Repairmentioning

confidence: 99%

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Glandular stem cells in the skin during development, homeostasis, wound repair and regeneration

Lin

2021

Experimental Dermatology

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“…To extrapolate information from underlying transcriptional networks, previous studies have employed several strategies to link cellular and molecular states to mammary epithelial identity. For example, combining flow cytometric isolation with functional cellular markers has improved our understanding of the dynamics of lineage commitment, differentiation processes and mammary tissue development [5,[14][15][16][17]. More recently, single-cell sequencing strategies have enabled the interpretation of contiguous cellular cues and epithelial lineage dynamics in the developing mammary gland [8,15,[18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland

Henry

Trousdell

Cyrill

et al. 2021

J Mammary Gland Biol Neoplasia

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The developing mammary gland depends on several transcription-dependent networks to define cellular identities and differentiation trajectories. Recent technological advancements that allow for single-cell profiling of gene expression have provided an initial picture into the epithelial cellular heterogeneity across the diverse stages of gland maturation. Still, a deeper dive into expanded molecular signatures would improve our understanding of the diversity of mammary epithelial and non-epithelial cellular populations across different tissue developmental stages, mouse strains and mammalian species. Here, we combined differential mammary gland fractionation approaches and transcriptional profiles obtained from FACS-isolated mammary cells to improve our definitions of mammary-resident, cellular identities at the single-cell level. Our approach yielded a series of expression signatures that illustrate the heterogeneity of mammary epithelial cells, specifically those of the luminal fate, and uncovered transcriptional changes to their lineage-defined, cellular states that are induced during gland development. Our analysis also provided molecular signatures that identified non-epithelial mammary cells, including adipocytes, fibroblasts and rare immune cells. Lastly, we extended our study to elucidate expression signatures of human, breast-resident cells, a strategy that allowed for the cross-species comparison of mammary epithelial identities. Collectively, our approach improved the existing signatures of normal mammary epithelial cells, as well as elucidated the diversity of non-epithelial cells in murine and human breast tissue. Our study provides a useful resource for future studies that use single-cell molecular profiling strategies to understand normal and malignant breast development.

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Targeting Tumor Heterogeneity by Breaking a Stem Cell and Epithelial Niche Interaction Loop

Ma,

Feng,

Chen

et al. 2024

Advanced Science

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Tumor heterogeneity, the presence of multiple distinct subpopulations of cancer cells between patients or among the same tumors, poses a major challenge to current targeted therapies. The way these different subpopulations interact among themselves and the stromal niche environment, and how such interactions affect cancer stem cell behavior has remained largely unknown. Here, it is shown that an FGF‐BMP7‐INHBA signaling positive feedback loop integrates interactions among different cell populations, including mammary gland stem cells, luminal epithelial and stromal fibroblast niche components not only in organ regeneration but also, with certain modifications, in cancer progression. The reciprocal dependence of basal stem cells and luminal epithelium is based on basal‐derived BMP7 and luminal‐derived INHBA, which promote their respective expansion, and is regulated by stromal‐epithelial FGF signaling. Targeting this interaction loop, for example, by reducing the function of one or more of its components, inhibits organ regeneration and breast cancer progression. The results have profound implications for overcoming drug resistance because of tumor heterogeneity in future targeted therapies.

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Heterotypic cell–cell communication regulates glandular stem cell multipotency

Cited by 102 publications

References 69 publications

Glandular stem cells in the skin during development, homeostasis, wound repair and regeneration

Glandular stem cells in the skin during development, homeostasis, wound repair and regeneration

Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland

Targeting Tumor Heterogeneity by Breaking a Stem Cell and Epithelial Niche Interaction Loop

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