Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing
© 2020 The Author(s) Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing to generate a detailed transcriptomic atlas...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/136089 |
| _version_ | 1826217642331996160 |
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| author | Li, Carman Man-Chung Shapiro, Hana Tsiobikas, Christina Selfors, Laura M Chen, Huidong Rosenbluth, Jennifer Moore, Kaitlin Gupta, Kushali P Gray, G Kenneth Oren, Yaara Steinbaugh, Michael J Guerriero, Jennifer L Pinello, Luca Regev, Aviv Brugge, Joan S |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Li, Carman Man-Chung Shapiro, Hana Tsiobikas, Christina Selfors, Laura M Chen, Huidong Rosenbluth, Jennifer Moore, Kaitlin Gupta, Kushali P Gray, G Kenneth Oren, Yaara Steinbaugh, Michael J Guerriero, Jennifer L Pinello, Luca Regev, Aviv Brugge, Joan S |
| author_sort | Li, Carman Man-Chung |
| collection | MIT |
| description | © 2020 The Author(s) Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing to generate a detailed transcriptomic atlas of young and aged murine mammary tissues. By analyzing epithelial, stromal, and immune cells, we identify age-dependent alterations in cell proportions and gene expression, providing evidence that suggests alveolar maturation and physiological decline. The analysis also uncovers potential pro-tumorigenic mechanisms coupled to the age-associated loss of tumor suppressor function and change in microenvironment. In addition, we identify a rare, age-dependent luminal population co-expressing hormone-sensing and secretory-alveolar lineage markers, as well as two macrophage populations expressing distinct gene signatures, underscoring the complex heterogeneity of the mammary epithelia and stroma. Collectively, this rich single-cell atlas reveals the effects of aging on mammary physiology and can serve as a useful resource for understanding aging-associated cancer risk. |
| first_indexed | 2024-09-23T17:06:56Z |
| format | Article |
| id | mit-1721.1/136089 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:06:56Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1360892023-01-27T21:17:45Z Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing Li, Carman Man-Chung Shapiro, Hana Tsiobikas, Christina Selfors, Laura M Chen, Huidong Rosenbluth, Jennifer Moore, Kaitlin Gupta, Kushali P Gray, G Kenneth Oren, Yaara Steinbaugh, Michael J Guerriero, Jennifer L Pinello, Luca Regev, Aviv Brugge, Joan S Massachusetts Institute of Technology. Department of Biology © 2020 The Author(s) Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing to generate a detailed transcriptomic atlas of young and aged murine mammary tissues. By analyzing epithelial, stromal, and immune cells, we identify age-dependent alterations in cell proportions and gene expression, providing evidence that suggests alveolar maturation and physiological decline. The analysis also uncovers potential pro-tumorigenic mechanisms coupled to the age-associated loss of tumor suppressor function and change in microenvironment. In addition, we identify a rare, age-dependent luminal population co-expressing hormone-sensing and secretory-alveolar lineage markers, as well as two macrophage populations expressing distinct gene signatures, underscoring the complex heterogeneity of the mammary epithelia and stroma. Collectively, this rich single-cell atlas reveals the effects of aging on mammary physiology and can serve as a useful resource for understanding aging-associated cancer risk. 2021-10-27T20:30:46Z 2021-10-27T20:30:46Z 2020 2021-07-22T15:38:26Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136089 en 10.1016/j.celrep.2020.108566 Cell Reports Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Li, Carman Man-Chung Shapiro, Hana Tsiobikas, Christina Selfors, Laura M Chen, Huidong Rosenbluth, Jennifer Moore, Kaitlin Gupta, Kushali P Gray, G Kenneth Oren, Yaara Steinbaugh, Michael J Guerriero, Jennifer L Pinello, Luca Regev, Aviv Brugge, Joan S Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing |
| title | Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing |
| title_full | Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing |
| title_fullStr | Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing |
| title_full_unstemmed | Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing |
| title_short | Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing |
| title_sort | aging associated alterations in mammary epithelia and stroma revealed by single cell rna sequencing |
| url | https://hdl.handle.net/1721.1/136089 |
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