Abstract

AbstractThe mammary gland is the distinct feature that gives the name to the class of mammals and distinguishes them from other animals. Functionally, the mammary gland is a secretory organ which main role is to produce milk to nourish the offspring. Organogenesis of the mammary gland starts during embryogenesis but occurs mainly after birth at puberty under the influence of hormonal cues. Throughout the adult life as well as during pregnancy, the mammary gland shows a remarkable regenerative ability, thus constituting an excellent model for studying stem cell biology. Although the mammary gland consists of a relatively simple epithelial structure with a luminal and a basal cell layers, these are indeed composed by distinct subsets of mammary epithelial cells. Flow cytometry and transplantation assay have identified several subpopulations of stem and/or progenitor cells in the mammary gland. Yet, physiological and developmental relevant information can only be obtained when investigating the stem cell hierarchy in the intact mammary gland. Genetic lineage tracing studies have offered unprecedented levels of information regarding the organization of the stem cell compartment and possible role of resident stem and/or progenitor cells at different stages of the mammary gland organogenesis. These studies, although creating a passionate debate, highlight the existence of heterogeneous stem cell compartment, where bipotent as well as unipotent mammary stem cells seems to co-exist. Genetic lineage tracing experiments provide relevant information on stem cells that are key for understanding both normal development as well as associated pathologies in human. It holds the promise of providing new insights into the cell-of-origin and heterogeneity of breast tumorigenesis.

Highlights

  • The mammary gland is a secretory organ, which main function is to produce milk that provides nutrition and immunological protection to the offspring

  • Genetic lineage tracing studies have offered unprecedented levels of information regarding the organization of the stem cell compartment and possible role of resident stem and/or progenitor cells at different stages of the mammary gland organogenesis

  • Genetic lineage tracing is the approach that it has been used for this purpose and has provided exciting knowledge of mammary gland organogenesis and homeostasis that provides unique information on how tissue turnover and repair is sustained

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Summary

Introduction

The mammary gland is a secretory organ, which main function is to produce milk that provides nutrition and immunological protection to the offspring. Mammary gland development starts at mid-gestation with the formation of the milk line, followed by generation of the mammary placodes and mammary buds. At around three to four weeks in the mouse, under influence of the ovarian hormones such as estrogen, the ends of the rudimentary ducts proliferate and form distinct multilayered epithelial structures known as the terminal end buds. These undergo successive rounds of elongation and bifurcation. Involution removes the milk-producing cells after lactation and remodels the mammary gland back to its pre-pregnancy state. A better understanding of the stem and progenitor cell populations provides useful insight into the mechanisms that sustain tissue turnover and repair upon injury as well as into human diseases such as cancer

Mammary epithelial cell types
Mammary stem cells in transplantation assay
Genetic lineage tracing
Constitutive Cre-LoxP recombination system
Inducible Cre-LoxP recombination systems
Inducible and reversible Tet recombination systems
The choice of the reporter
Genetic lineage tracing in the mammary gland
Mammary stem cell hierarchy revealed by genetic lineage tracing
Genetic lineage tracing in breast cancer
Conclusion
Full Text
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