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Status |
Public on Oct 11, 2012 |
Title |
Elucidating the gene expression profiles of human mammary subpopulations |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
The organisation of the mammary epithelial cell hierarchy and how these cells relate to the presentation of human breast tumours is poorly understood. Our results demonstrate that the luminal cell compartment of the mouse mammary gland can be resolved into terminally differentiated oestrogen receptor (ER)+ luminal cells, ER+ luminal progenitors and ER- luminal progenitors. The ER+ luminal progenitors are unique in regards to cell survival, as they are relatively insensitive to loss of oestrogen and progesterone when compared to the other types of mammary epithelial cells. Analysis of normal human breast tissue reveals a similar hierarchical organisation that is composed of terminally differentiated luminal cells and relatively differentiated (EpCAM+CD49f+ALDH-) and undifferentiated (EpCAM+CD49f+ALDH+) luminal progenitors. In addition, approximately one third of human breast samples examined contained an additional population that had a luminal progenitor phenotype, but is characterised by low expression of ERBB3 and low proliferative potential. Parent-progeny relationship experiments demonstrated that all luminal progenitor populations in both species are highly plastic and, at low frequencies, can generate progeny representing all mammary cell types. Gene expression profiling demonstrates that the ER- luminal progenitors in the mouse and the undifferentiated ALDH+ luminal progenitors in the human have gene signatures that resemble those obtained from basal-like breast tumours. Overall, our work reveals a more defined mammary cell hierarchy, which may in turn provide greater insight into the aetiology of breast cancer.
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Overall design |
Normal human breast tissues from reduction mammoplasties were dissociated into single cells and the epithelial cell populations were flow sorted. Total RNA was extracted for each group in 11 independent patient samples.
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Contributor(s) |
Shehata M, Stingl J, Russell R |
Citation(s) |
23088371 |
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Submission date |
Jan 29, 2012 |
Last update date |
Aug 13, 2018 |
Contact name |
Roslin Russell |
E-mail(s) |
[email protected]
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Phone |
01223 769770
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Organization name |
Cambridge Research Institute, Cancer Research UK
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Street address |
Robinson Way
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City |
Cambridge |
ZIP/Postal code |
CB2 0RE |
Country |
United Kingdom |
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Platforms (1) |
GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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Samples (72)
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Relations |
BioProject |
PRJNA152785 |