Rare somatic cells from human breast tissue exhibit extensive lineage plasticity

Roy, Somdutta; Gascard, Philippe; Dumont, Nancy; Zhao, Jianxin; Pan, Deng; Petrie, Sarah; Margeta, Marta; Tlsty, Thea D.

doi:10.1073/pnas.1218682110

Cited by 80 publications

(81 citation statements)

References 34 publications

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“…Initial investigations indicated that cells positive for pluripotency genes are present in the mammary epithelium, both its ductal and alveolar compartments, and in substantially larger numbers during lactation than in the resting breast (18,54). This further supports a role for these cells and the pluripotency genes they express in the remodeling of the mammary gland toward a milk-secretory organ.…”

Section: Breast Milk Stem Cellsmentioning

confidence: 83%

“…In both cases, indirect evidence supports the notion that they play critical roles. In the mammary gland, they appear to be important during its remodeling toward a milk-secretory organ, as is suggested by the higher expression of pluripotency genes during pregnancy, when epithelial expansion occurs, and the rarity of these cells in the resting breast (18,54). In the infant, the substantial number of these stem cells ingested daily during breastfeeding (thousands to millions) implies a function (2).…”

Section: Functions Of Breast Milk Stem Cellsmentioning

confidence: 99%

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At the Dawn of a New Discovery: The Potential of Breast Milk Stem Cells

Hassiotou

Hartmann

2014

Advances in Nutrition

102

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Breast milk contains bioactive molecules that provide a multitude of immunologic, developmental and nutritional benefits to the infant. Less attention has been placed on the cellular nature of breast milk, which contains thousands to millions of maternal cells in every milliliter that the infant ingests. What are the properties and roles of these cells? Most studies have examined breast milk cells from an immunologic perspective, focusing specifically on the leukocytes, mainly in the early postpartum period. In the past decade, research has taken a multidimensional approach to investigating the cells of human milk. Technologic advances in single cell analysis and imaging have aided this work, which has resulted in the breakthrough discovery of stem cells in breast milk with multilineage potential that are transferred to the offspring during breastfeeding. This has generated numerous implications for both infant and maternal health and regenerative medicine. This review summarizes the latest knowledge on breast milk stem cells, and discusses their known in vitro and in vivo attributes as well as potential functions and applications.

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Section: Breast Milk Stem Cellsmentioning

confidence: 83%

Section: Functions Of Breast Milk Stem Cellsmentioning

confidence: 99%

At the Dawn of a New Discovery: The Potential of Breast Milk Stem Cells

Hassiotou

Hartmann

2014

Advances in Nutrition

102

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“…À in adult human breasts (Roy et al 2013). The presence of pluripotent cells in the adult gland (Hassiotou et al 2012;Roy et al 2013) or the possible persistence of fetal MaSCs into adulthood has profound implications for breast oncogenesis.…”

Section: Heterogeneity Within the Masc Populationmentioning

confidence: 99%

“…The presence of pluripotent cells in the adult gland (Hassiotou et al 2012;Roy et al 2013) or the possible persistence of fetal MaSCs into adulthood has profound implications for breast oncogenesis. It is relevant that an embryonic stem cell-like expression profile may be associated with poorly differentiated, aggressive breast tumors (Ben-Porath et al 2008).…”

Section: Heterogeneity Within the Masc Populationmentioning

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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“…Whether these stem/progenitor cell markers identify the same cell populations remains unknown. Furthermore, Tlsty and colleagues discovered that human breast cells can exhibit extensive lineage plasticity (7), which may explain why marker profiles have been difficult to associate with distinct tumor subtypes.…”

Section: Introductionmentioning

confidence: 99%

Taxonomy of breast cancer based on normal cell phenotype predicts outcome

Santagata¹,

Thakkar²,

Ergonul³

et al. 2014

J. Clin. Invest.

172

214

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Accurate classification is essential for understanding the pathophysiology of a disease and can inform therapeutic choices. For hematopoietic malignancies, a classification scheme based on the phenotypic similarity between tumor cells and normal cells has been successfully used to define tumor subtypes; however, use of normal cell types as a reference by which to classify solid tumors has not been widely emulated, in part due to more limited understanding of epithelial cell differentiation compared with hematopoiesis. To provide a better definition of the subtypes of epithelial cells comprising the breast epithelium, we performed a systematic analysis of a large set of breast epithelial markers in more than 15,000 normal breast cells, which identified 11 differentiation states for normal luminal cells. We then applied information from this analysis to classify human breast tumors based on normal cell types into 4 major subtypes, HR0-HR3, which were differentiated by vitamin D, androgen, and estrogen hormone receptor (HR) expression. Examination of 3,157 human breast tumors revealed that these HR subtypes were distinct from the current classification scheme, which is based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Patient outcomes were best when tumors expressed all 3 hormone receptors (subtype HR3) and worst when they expressed none of the receptors (subtype HR0). Together, these data provide an ontological classification scheme associated with patient survival differences and provides actionable insights for treating breast tumors.

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Rare somatic cells from human breast tissue exhibit extensive lineage plasticity

Abstract: We identified cell surface markers associated with repression of p16 INK4a

Cited by 80 publications

References 34 publications

At the Dawn of a New Discovery: The Potential of Breast Milk Stem Cells

At the Dawn of a New Discovery: The Potential of Breast Milk Stem Cells

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

Taxonomy of breast cancer based on normal cell phenotype predicts outcome

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