Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages

Sale, Sanja; Lafkas, Daniel; Artavanis‐Tsakonas, Spyros

doi:10.1038/ncb2725

Cited by 71 publications

(62 citation statements)

References 36 publications

(30 reference statements)

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“…Notch2 has recently been implicated in patterning of the tertiary branches and formation of alveolar clusters [155]. Given the role of progesterone in tertiary branching and alveologenesis, it would be interesting to determine whether Notch2 + cells are also PR + or in close proximity to PR + cells.…”

Section: Parity and Progenitor Cell Populationsmentioning

confidence: 99%

Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy

Arendt

Kuperwasser

2015

J Mammary Gland Biol Neoplasia

102

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The mammary gland undergoes dramatic post-natal growth beginning at puberty, followed by full development occurring during pregnancy and lactation. Following lactation, the alveoli undergo apoptosis, and the mammary gland reverses back to resemble the nonparous gland. This process of growth and regression occurs for multiple pregnancies, suggesting the presence of a hierarchy of stem and progenitor cells that are able to regenerate specialized populations of mammary epithelial cells. Expansion of epithelial cell populations in the mammary gland is regulated by ovarian steroids, in particular estrogen acting through its receptor estrogen receptor alpha (ERα) and progesterone signaling through progesterone receptor (PR). A diverse number of stem and progenitor cells have been identified based on expression of cell surface markers and functional assays. Here we review the current understanding of how estrogen and progesterone act together and separately to regulate stem and progenitor cells within the human and mouse mammary tissues. Better understanding of the hierarchal organization of epithelial cell populations in the mammary gland and how the hormonal milieu affects its regulation may provide important insights into the origins of different subtypes of breast cancer.

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Section: Parity and Progenitor Cell Populationsmentioning

confidence: 99%

Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy

Arendt

Kuperwasser

2015

J Mammary Gland Biol Neoplasia

102

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“…This model could also explain the observations made in diffuse large B-cell lymphomas [2] and other cancers that contain intrinsic subtypes. It is possible to use a technique known as 'lineage tracing' to identify the candidate cell(s) of origin in tumors in genetically engineered mouse models [9][10][11], but it is not clear that the…”

Section: Introductionmentioning

confidence: 99%

Genetic subtypes of invasive bladder cancer

McConkey

Choi

Dinney

2015

Current Opinion in Urology

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Like their breast cancer counterparts, basal bladder cancers are characterized by poor clinical outcomes in the absence of effective systemic therapy, but a large fraction of them do respond to neoadjuvant chemotherapy, suggesting that the tumors should be managed aggressively. On the contrary, tumors that belong to the 'p53-like' subtype tend to be chemoresistant, so patients with these tumors should probably be managed differently. It seems likely that prospective identification of tumor intrinsic subtype membership could complement the use of DNA-based biomarkers to identify the groups of patients who will benefit the most from chemotherapy and targeted agents.

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“…Such cells also contributed to alveolar structures in a polyclonal fashion and could survive multiple rounds of pregnancy, reminiscent of PI-MECs. Lineage tracing studies of another member of this gene family, Notch2, identified two previously unrecognized cell types in the luminal lineage (Sale et al 2013). The large (L) and small (S) cells described were both exceedingly rare, since they constituted <1% of the total mammary epithelium.…”

Section: Identification Of Luminal Progenitor Cells Via Lineage Tracingmentioning

confidence: 99%

Mammary stem cells and the differentiation hierarchy: current status and perspectives

2014

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The mammary epithelium is highly responsive to local and systemic signals, which orchestrate morphogenesis of the ductal tree during puberty and pregnancy. Based on transplantation and lineage tracing studies, a hierarchy of stem and progenitor cells has been shown to exist among the mammary epithelium. Lineage tracing has highlighted the existence of bipotent mammary stem cells (MaSCs) in situ as well as long-lived unipotent cells that drive morphogenesis and homeostasis of the ductal tree. Moreover, there is accumulating evidence for a heterogeneous MaSC compartment comprising fetal MaSCs, slow-cycling cells, and both long-term and short-term repopulating cells. In parallel, diverse luminal progenitor subtypes have been identified in mouse and human mammary tissue. Elucidation of the normal cellular hierarchy is an important step toward understanding the “cells of origin” and molecular perturbations that drive breast cancer.

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Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages

Cited by 71 publications

References 36 publications

Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy

Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy

Genetic subtypes of invasive bladder cancer

Mammary stem cells and the differentiation hierarchy: current status and perspectives

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