Embryonic mammary gland stem cells identified

May 22, 2018

Publication in Nature Cell Biology: researchers at the Université libre de Bruxelles, ULB define for the first time the mechanisms responsible for the mammary gland development.

The mammary gland is the tissue that produces the milk during lactation, allowing the survival of young mammalian offspring. The mammary gland is composed of two main lineages: the basal cells, which surround the inner luminal cells. The luminal cells can be subdivided into ductal cells, and alveolar cells that produce the milk. The basal cells allow the circulation of the milk from the alveoli to the nipple region through their contractile properties. During pubertal mammary gland expansion and adult life, distinct pools of unipotent stem cells replenish the basal and luminal lineages independently of each other's. However, it remains unclear how mammary gland initially develops. Are embryonic mammary gland progenitors multipotent, meaning that their progenitors are capable of giving rise to both basal and luminal cells? If so, when does the switch from multipotency to unipotency occur? And what are the molecular mechanisms that regulate multipotency and basal and luminal lineage segregation?

In a new study published in Nature Cell Biology, research team led by Prof. Cédric Blanpain, MD/PhD, WELBIO investigator and Professor at the Université libre de Bruxelles, Belgium, identified the mechanisms that regulate mammary gland development. Using a combination of lineage tracing, molecular profiling, single cell sequencing and functional experiments, Aline Wuidart and colleagues demonstrated that mammary gland initially develops from multipotent progenitors during the early steps of embryonic mammary gland morphogenesis whereas postnatal mammary gland development is mediated by lineage-restricted stem cells.

To understand the molecular mechanisms regulating multipotency during embryonic development, the researchers developed a novel strategy to isolate embryonic mammary gland stem cells, and assessed for the first time their molecular features using single cell sequencing in collaboration with Thierry Voet group, KUL/Sanger Institute. Interestingly, only embryonic mammary gland progenitors and not adult cells, expressed a hybrid transcriptional signature comprising markers for both luminal and basal lineages, explaining their multipotent fate at this stage of embryonic development.

Breast cancer is the most common cancer among women. By analyzing the early steps of breast cancer formation, Alexandra Van Keymeulen and Cédric Blanpain previously demonstrated that the expression of one of the most frequently mutated genes in patients with breast cancers reactivates a multipotent program in adult unipotent stem cells. In this new study, the researchers show that embryonic mammary gland progenitors express the same genes than during the reactivation of multipotency associated with breast cancer development. "It was really interesting to see that many genes found to be specifically expressed by embryonic mammary gland progenitors are expressed in aggressive human breast cancers with poor prognosis, further suggesting that the reactivation of a gene expression program characteristic of embryonic mammary gland during tumorigenesis is essential for cancer growth and invasion." Comments Cédric Blanpain, the senior author of this study.

In conclusion, this new study identifies multipotent embryonic stem cells of the mammary gland, uncovers the molecular features associated with embryonic multipotency and identifies the molecular mechanisms regulating the switch from multipotency to unipotency during mammary gland development. The paradigm uncovered in this study has important implications for the understanding of the development of other glandular organs and tissues such as the prostate that present similar developmental switch. Finally, the mechanisms uncovered here have also implications for cancer development and progression.
-end-


Université libre de Bruxelles

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.