Dynamics, function, and regulation of mammary stem cells in development and disease - review article

Sep 22, 2026

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Understanding the heterogeneity of mammary epithelial cells and their roles in postnatal development, regeneration, and disease is crucial. Recent advances clarify the intrinsic complexity of the mammary epithelium, its interactions with stroma, and the origins and behaviors of adult stem and progenitor cells. These insights refine normal mammary gland biology and identify epithelial subsets as sources and targets in breast cancer. The review synthesizes mechanisms linking mammary stem cells and tumor-initiating cells, emphasizing niche components, key signaling pathways, and how developmental programs are redirected during malignant progression.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Mammary gland as a postnatal developmental model

Epithelial-stromal composition and remodeling across life stages

Comparison between mouse and human mammary architecture

Review scope and framework

Linking development to tumorigenesis via stemness and plasticity

[www.nature.com/emm](www.nature.com/emm) REVIEW ARTICLE OPEN Dynamics, function, and regulation of mammary stem cells in development and disease Eunmi Lee1,2,3, Yujie Tao1,2, Alice J. Wang 1,2 and Yibin Kang 1,2,4 ✉ © The Author(s) 2026 | | | | | --- | --- | --- | | | Understanding the heterogeneity of mammary epithelial cells and their contributions to postnatal development and regeneration is of great importance. Recent advances have deﬁned the intrinsic complexity of the mammary epithelium, its stromal interactions, and the ontogeny of adult stem and progenitor cells. These insights have not only reﬁned our understanding of normal mammary gland biology but also highlighted how speciﬁc epithelial subsets serve as cells of origin and targets of transformation in breast cancer. The close parallels between mammary stem cells and tumor-initiating cells, particularly their shared plasticity and selfrenewal, highlight stemness as a central node linking developmental programs to malignant transformation. Both populations are shaped by microenvironmental cues and specialized niche components that regulate their maintenance, fate, and susceptibility tooncogenic reprogramming. Here, we review recent advances in mammary epithelial biology, emphasizing the key signaling pathways and stromal interactions that govern mammary stem cell behavior during development and tumorigenesis. We further discuss how developmental programs and microenvironmental cues that sustain mammary morphogenesis are subverted during cancer progression, with particular attention to pregnancy-associated transient susceptibility and aging-associated cancer risk. Overall, this Review offers a framework for understanding how normal mammary epithelial programs are redirected during | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | malignant progression. | | | | | Experimental & Molecular Medicine (2026) 58:2407–2416; [https://doi.org/10.1038/s12276-026-01780-6](https://doi.org/10.1038/s12276-026-01780-6) | | | | | | INTRODUCTION The mammary gland represents a unique model of postnatal organ development, whose primary physiological role is milk production for offspring nourishment1–3. Structurally, it is composed of epithelial, adipose, and various stromal cells, including ﬁbroblasts, endothelial cells, and immune cells that work in concert to achieve this function4. The mammary gland undergoes much of its morphogenesis after birth. In the mouse, ﬁve pairs of rudimentary epithelial placodes arise from the ectoderm around embryonic day 10.5 and expand until embryonic day 18, after which further growth is largely restricted until puberty1. At puberty, extensive ductal elongation and branching morphogenesis occur, forming a mature ductal tree that continues to remodel throughout adulthood in response to hormonal and physiological cues. Ductal outgrowth is driven by club-shaped, highly proliferative terminal end buds (TEBs) that invade the adipose-rich mammary fat pad. Each TEB consists of an outer layer of cap cells, which give rise to basal myoepithelial cells, and an inner layer of body cells, which differentiate into luminal cells. As ductal elongation completes and the growing tips reach the boundary of the mammary fat pad, TEBs regress, leaving a mature ductal network composed of primary ducts, secondary branches, and tertiary side branches that extend laterally to ﬁll the gland5. Cyclical remodeling of the mammary epithelium continues throughout life. The mature gland remains remarkably dynamics, undergoing periodic structural and functional changes in response to hormonal ﬂuctuations. During estrus cycle, subtle rounds of ductal budding and regression occur, maintaining epithelial turnover and plasticity. With pregnancy, the gland undergoes extensive lobuloalveolar expansion as luminal progenitors (LPs) proliferate and differentiate into milk-secreting alveolar c

FAQs

What is the main focus of this review article?

The review focuses on the dynamics, functions, and regulation of mammary stem cells during development and disease, including how signaling pathways and stromal interactions shape stem cell behavior and contribute to tumorigenesis.

How do mammary stem cells relate to tumor-initiating cells?

The article highlights close parallels between mammary stem cells and tumor-initiating cells, especially shared plasticity and self-renewal, linking developmental programs to malignant transformation.

How does the mammary gland change across key life stages mentioned in the text?

It undergoes ductal growth and branching at puberty, cyclic remodeling during the estrus cycle, extensive lobuloalveolar expansion during pregnancy with differentiation for milk production, and coordinated involution after lactation with epithelial apoptosis and tissue remodeling.

Sep 22, 2026

Upload by acoobca