Age-related gene expression in luminal epithelial cells is driven by a microenvironment made from myoepithelial cells

Miyano, Masaru; Sayaman, Rosalyn W.; Stoiber, Marcus H.; Lin, Chun-Han; Stampfer, Martha R.; Brown, James H.; LaBarge, Mark A.

doi:10.18632/aging.101298

Cited by 19 publications

(61 citation statements)

References 57 publications

(66 reference statements)

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“…This suggests a deregulation of gene expression with age (Miyano et al 2017;Yau et al 2007). Our data confirm a loss of regulation manifested by the lack in response to ECM in HMEC derived from ageing women.…”

Section: Yarwood and Woodgett 2001) Other Researchers Have Found Greatsupporting

confidence: 76%

“…The fate of the progenitor mammary cell, whether it turns into a luminal or myoepithelial cell, is determined by a combination of soluble signals from other cells, as well as the surrounding extracellular matrix which together make up the microenvironment (LaBarge et al 2009;Lui et al 2012;Lim et al 2009;Miyano et al 2017). The sensing of the cellular microenvironment comprises cell-cell and cell-ECM interactions, as well as interactions with soluble and tensile factors (Glukhova & Streuli 2013).…”

Section: Mammary Microenvironmentmentioning

confidence: 99%

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Microsphere cytometry to interrogate microenvironment-dependent cell signaling

et al. 2017

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2018Avhandling for graden philosophiae doctor (ph.d.)Dato for disputas: 06.04.18Trykk:Skipnes Kommunikasjon / Universitetet i Bergen Materialet i denne publikasjonen er omfattet av åndsverkslovens bestemmelser. Tittel:The effects of ageing on microenvironment-contextual epithelial cell signalling Rein Aasland, for valuable insight on academic writing, and for pointing out, as did James, when my words became self-indulgent fun and flowers. Mark LaBarge, for taking me into his lab, and letting me partake in that which concerns absolutely everyone: ageing. To Martha Stampfer for allowing me to poke around in her human cell resources biobank. To James Garbe for being an incredibly sympathetic guy with the most convenient knowledge up his sleeve.I would like to thank my mother Nina-Mamma for never curbing her enthusiasm for tiny biology when I brought home science homework, and my father Ulf for being genuinely impressed with pretty much everything I didincluding when I did it badly. I need to thank my boyfriend, Lars, for meticulous proofreading of the manuscript, and for continuously encouraging me to put my academic whims into writing. I want to point out that Iren Abrahamsen did substantial preliminary work for the microsphere cytometry method. I need to to thank my medical doctor office mates, Gry and Kjersti for valuable insights from the clinical realm where lab rats never go, to remind me who we're doing this for in the first place. Thanks to Sissel for being that steady rock in the corner stall of the lab where PhDs and postdocs fly by. I would like to thank the girls in the lab for taking up the fight against cancer cell Fråtse-Frida, and winning it. Finally, I would like to thank the Cancer Society, VilVite, CCBIO and Forskningsdagene for giving me trust, whether it was to develop flow cytometry protocols or popular science shows, or to interrogate the microenvironment I would like thank just anyone else in the lab and the general world who is interested and willing to contemplate big ideas such as the purpose of being. And at last, every single nerd: nerdy boys and nerdy girls. pathway activation levels in HMEC are attenuated with age, and that the diminished signaling magnitude in HMEC from ageing women correlated with reduced probability of activating oncogene-induced senescence.Our results suggest that attenuated cell signaling response may reduce the likelihood of activating oncogene induced senescence, for cells in ageing women. We hypothesize this is the result of age-related changes to the microenvironment that support age-emergent cellular phenotypes with increased cancer susceptibility.

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Section: Yarwood and Woodgett 2001) Other Researchers Have Found Greatsupporting

confidence: 76%

Section: Mammary Microenvironmentmentioning

confidence: 99%

Microsphere cytometry to interrogate microenvironment-dependent cell signaling

et al. 2017

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“…This is the first study to use a WGBS approach to examine the impact of age on the DNA methylome of primary human mammary epithelial cells. Previous studies were done using array-based technologies that cover only a fraction of the CpG sites in the genome (Miyano et al 2017;Hofstatter et al 2018;Castle et al 2020). Importantly, repeat elements are under-represented in these array probes (Bell et al 2019), making interpretation of DNA methylation at repetitive regions difficult.…”

Section: Discussionmentioning

confidence: 99%

“…Tissues were obtained from women with differing chronological ages but without breast cancer. These pre-stasis LEPs from primary cultures maintain gene expression and DNA methylation profiles that mirror those in tissue (Miyano et al 2017). Moreover, these are nonsenescent cells and therefore are a valuable resource that can be used to interrogate aging dependent changes in the breast tissue -distinct from those arising from in vitro cellular senescence.…”

Section: Aging Leads To Altered Dna Methylation Patterns In Mammary Lmentioning

confidence: 99%

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Aging leads to DNA methylation alterations associated with loss of lineage fidelity and breast cancer in mammary luminal epithelial cells

Senapati

Miyano

Sayaman

et al. 2020

Preprint

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The aging process is characterized by an accumulation of cellular damage, including alterations to the epigenome. While it is clear that DNA methylation patterns change with age, the mechanisms behind these epigenomic alterations - and their functional consequences - have remained unclear. One of the primary roles of DNA methylation in mammalian genomes is in the repression of retrotransposons. Many of these repetitive elements contain regulatory sequences, and loss of repression can lead to aberrant transcriptional regulation. Aging-associated DNA methylation loss at transposable elements (TEs), therefore, has the potential to rewire gene expression networks to be favorable for pathologies, including age-related diseases such as cancer. However, the extent of loss of epigenetic silencing at transposable elements during aging and the functional consequences of this have remained unclear. Luminal epithelial cells in the breast tissue are a key cell lineage implicated in age-related luminal breast cancers. We report here that aging leads to distinct DNA methylation patterns at tissue-specific regulatory elements and TEs in luminal epithelial cells. DNA methylation changes at regulatory elements are driven by altered activity of lineage-specific transcription factors such as ELF5 and TP63. However, transposable elements, especially recently evolved TEs, exhibit stochastic loss of methylation and increased methylation entropy with age. TEs that lose methylation with age regulate known breast cancer genes and are associated with elevated breast cancer risk. Altogether, our results indicate that aging leads to DNA methylation loss at evolutionarily young TEs that can impact gene networks important for age-related breast cancers.

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Age-related gene expression in luminal epithelial cells is driven by a microenvironment made from myoepithelial cells

Cited by 19 publications

References 57 publications

Microsphere cytometry to interrogate microenvironment-dependent cell signaling

Microsphere cytometry to interrogate microenvironment-dependent cell signaling

Aging leads to DNA methylation alterations associated with loss of lineage fidelity and breast cancer in mammary luminal epithelial cells

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