Faculty Opinions recommendation of Multiscale imaging of basal cell dynamics in the functionally mature mammary gland.

SUMMARYOur knowledge of transcriptional heterogeneities in epithelial stem/progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem/progenitor potential, but a non-biased dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA-sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell transcriptional states in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses produce a quasi-linear differentiation hierarchy where basal cells progress from Col17a1high/Trp63high state to early response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal states. Our study provides a systematic view of epidermal cellular dynamics supporting a revised “hierarchical-lineage” model of homeostasis.

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Transcription Factor RFX3 Stabilizes Mammary Basal Cell Identity

10.1101/2021.12.13.472491 ◽

2021 ◽

Author(s):

Ian Macara ◽

Erica M. Tross ◽

Christian de Caestecker ◽

Ken Lau

Keyword(s):

Mammary Gland ◽

Basal Cell ◽

Regulatory Networks ◽

Cell Tracking ◽

Molecular Mechanisms ◽

Myoepithelial Cells ◽

Mammary Fat Pad ◽

Transplantation Assay ◽

Differential Gene

The myoepithelial cell compartment of the murine postnatal mammary gland is generated from basal cap cells in the terminal end bud and maintained by self-renewal. Transdifferentiation to the luminal lineage does not normally occur but can be induced by DNA damage, luminal cell death or transplantation into a recipient mammary fat pad. Myoepithelial cells cultivated in vitro can also transdifferentiate towards the luminal lineage. Little is known about the molecular mechanisms and gene regulatory networks underlying this plasticity. Using a transgenic mouse (Tg11.5kb-GFP) that marks cap cells with GFP, we discovered that mature myoepithelial cells placed in culture begin to express GFP within ~24 hrs and later express the Keratin 8 (K8) luminal marker. Cell tracking showed that most K8+ cells arose from GFP+ cells, suggesting that myoepithelial cells de-differentiate towards a progenitor state before changing lineage. Differential gene expression analysis, comparing pure GFP+ cap cells with mature myoepithelial cells, identified multiple transcription factors that iRegulon predicted might regulate the myoepithelial to cap cell transition. Knockout of one of these genes, Regulatory Factor 3 (Rfx3), significantly reduced the population of GFP+ cells and increased differentiation to the K8+ luminal lineage. Rfx3 knockout also reduced mammosphere growth and mammary gland regeneration efficiency in a transplantation assay, but had no effect on proliferation in vitro. Together, these data support a key role for Rfx3 in the stabilization of the mammary basal cell lineages.

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Multiscale imaging of basal cell dynamics in the functionally mature mammary gland

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2016905117 ◽

2020 ◽

Vol 117 (43) ◽

pp. 26822-26832 ◽

Cited By ~ 5

Author(s):

Alexander J. Stevenson ◽

Gilles Vanwalleghem ◽

Teneale A. Stewart ◽

Nicholas D. Condon ◽

Bethan Lloyd-Lewis ◽

...

Keyword(s):

Mammalian Species ◽

Mammary Epithelium ◽

Physiological Signals ◽

Cell Dynamics ◽

Positive Displacement ◽

Mammary Cell ◽

Innermost Layer ◽

Multidimensional Imaging ◽

Luminal Cells ◽

Multiscale Imaging

The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network. Using quantitative, multidimensional imaging of mammary cell ensembles from GCaMP6 transgenic mice, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk begins its passage toward the dependent neonate, seconds after the command.

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Spontaneous Basaloid Adenomas of the Mammary Gland in Four Dogs: Clinicopathologic and Immunohistochemical Features

Veterinary Pathology ◽

10.1354/vp.39-6-739 ◽

2002 ◽

Vol 39 (6) ◽

pp. 739-743 ◽

Cited By ~ 4

Author(s):

J. Martín de las Mulas ◽

J. Ordás ◽

M. Y. Millán ◽

A. Espinosa de los Monteros ◽

C. Reymundo

Keyword(s):

Estrogen Receptor ◽

Mammary Gland ◽

Epithelial Cells ◽

Tumor Cells ◽

Basal Cell ◽

Estrogen Receptor Alpha ◽

Progesterone Receptors ◽

Receptor Alpha ◽

Contraceptive Steroids

Spontaneous basaloid adenomas occurred in four out of 354 dogs with mammary tumors. Affected dogs were pure-bred, intact females between 6 and 8 years of age. Three dogs were nuliparous, two had pseudopregnancies, and none had received contraceptive steroids. The tumors were multiple (three cases) or unique, less than 1 cm in diameter, well delineated, and composed of uniform cords and clusters of monomorphic epithelial cells with focal signs of squamous or glandular differentiation. A basal cell immunophenotype (cytokeratins 5 and 14 positive) without either glandular epithelial (cytokeratins 8, 18, and 19 negative) or myoepithelial (calponin negative) differentiation was observed in the majority of tumor cells. No recurrence or metastasis was recorded after follow-up periods between 3 and 24 months. In spite of the hormone-dependent nature of this tumor in female Beagles given experimental contraceptive steroids, spontaneous basaloid adenomas lacked estrogen receptor alpha and progesterone receptors.

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Immunohistochemical investigation into the distribution pattern of myoepithelial cells in the bovine mammary gland

Journal of Dairy Research ◽

10.1017/s0022029997002148 ◽

1997 ◽

Vol 64 (2) ◽

pp. 197-205 ◽

Cited By ~ 10

Author(s):

EVA HELLMÉN ◽

AXEL ISAKSSON

Keyword(s):

Smooth Muscle ◽

Mammary Gland ◽

Distribution Pattern ◽

Basal Cell ◽

Cell Layer ◽

Smooth Muscle Actin ◽

Myoepithelial Cells ◽

Muscle Actin ◽

Bovine Mammary Gland ◽

Basal Cell Layer

The distribution pattern of myoepithelial cells in the bovine mammary gland was investigated by an immunohistochemical technique, using monoclonal antibodies against cytokeratins 5, 6 and 18 and cytokeratins 8 and 14 and against α-smooth-muscle actin filaments. Myoepithelial cells were shown to be present as a continuous basal cell layer in the intralobular ducts, as discontinuous cell rows in the basal cell layer of the interlobular ducts, and as single cells dispersed in the basal cell layer of the quarter cisterns, while they were apparently absent in the teat cisterns. Unlike the case with myoepithelial cells of the human breast, anti-cytokeratin 14 was less specific as a marker of bovine myoepithelial cells than was anti-α-smooth-muscle actin.

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284 Slug Controls P-cadherin and Regulates Stem/progenitor Cell Dynamics During Mammary Gland Morphogenesis

European Journal of Cancer ◽

10.1016/s0959-8049(12)70979-6 ◽

2012 ◽

Vol 48 ◽

pp. S69-S70

Author(s):

Y. Idoux-Gillet ◽

M. Nassour ◽

A. Selmi ◽

C. Come ◽

M.A. Deugnier ◽

...

Keyword(s):

Mammary Gland ◽

Progenitor Cell ◽

Cell Dynamics ◽

Mammary Gland Morphogenesis ◽

Gland Morphogenesis

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TBX1 and Basal Cell Carcinoma: Expression and Interactions with Gli2 and Dvl2 Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms21020607 ◽

2020 ◽

Vol 21 (2) ◽

pp. 607 ◽

Cited By ~ 2

Author(s):

Cinzia Caprio ◽

Silvia Varricchio ◽

Marchesa Bilio ◽

Federica Feo ◽

Rosa Ferrentino ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Adaptor Protein ◽

Cellular Model ◽

Cell Dynamics ◽

Healthy Human ◽

Shh Signaling ◽

Signaling Systems ◽

Multipotent Progenitor Cells

Early events of basal cell carcinoma (BCC) tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of Patched1 (Ptch1) or by activating mutations of Smoothened (Smo). TBX1 is a key regulator of pharyngeal development, mainly through expression in multipotent progenitor cells of the cardiopharyngeal lineage. This transcription factor is connected to several major signaling systems, such as FGF, WNT, and SHH, and it has been linked to cell proliferation and to the regulation of cell shape and cell dynamics. Here, we show that TBX1 was expressed in all of the 51 BCC samples that we have tested, while in healthy human skin it was only expressed in the hair follicle. Signal intensity and distribution was heterogeneous among tumor samples. Experiments performed on a cellular model of mouse BCC showed that Tbx1 is downstream to GLI2, a factor in the SHH signaling, and that, in turn, it regulates the expression of Dvl2, which encodes an adaptor protein that is necessary for the transduction of WNT signaling. Consistently, Tbx1 depletion in the cellular model significantly reduced cell migration. These results suggest that TBX1 is part of a core transcription network that promotes BCC tumorigenesis.

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Mammary gland in vulva (rare clinical case)

Kazan medical journal ◽

10.17816/kmj1724 ◽

2012 ◽

Vol 93 (5) ◽

pp. 838-840

Author(s):

L A Kozlov ◽

V I Zhuravleva

Keyword(s):

Mammary Gland ◽

Breast Milk ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Histological Examination ◽

Basal Cell ◽

Clinical Case ◽

The Right ◽

Labium Majus

A rare clinical case of a patient with fibroadenoma of the vulva’s right labium majus with a typical hystological structure of mammary grand is described. The patient noticed a tumor of the right labium majus approximately 10 years before admission. After the childbirth while breastfeeding patient noticed a whitish discharge form the tumor which looked like breast milk. At the oncologic dispensary biopsy was performed after the tumor punction, atypical basal epithelium was found, and the basal cell carcinoma was suspected. Histological examination revealed fibroadenoma with a typical hystological structure of mammary grand.

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