scholarly journals Stem Cells and the Differentiation Hierarchy in Mammary Gland Development

2020 ◽  
Vol 100 (2) ◽  
pp. 489-523 ◽  
Author(s):  
Nai Yang Fu ◽  
Emma Nolan ◽  
Geoffrey J. Lindeman ◽  
Jane E. Visvader
Keyword(s):  
Stem Cells ◽  
Mammary Gland ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Large Scale ◽  
Mammary Epithelium ◽  
Mammary Stem ◽  
Stem And Progenitor Cells ◽  
Intrinsic Complexity ◽  
Small Pool

The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within the epithelial hierarchy. While unipotent progenitor cells predominantly execute day-to-day homeostasis and postnatal morphogenesis during puberty and pregnancy, multipotent MaSCs have been implicated in coordinating alveologenesis and long-term ductal maintenance. Nonetheless, the multipotency of stem cells in the adult remains controversial. The advent of large-scale single-cell molecular profiling has revealed striking changes in the gene expression landscape through ontogeny and the presence of transient intermediate populations. An increasing number of lineage cell-fate determination factors and potential niche regulators have now been mapped along the hierarchy, with many implicated in breast carcinogenesis. The emerging diversity among stem and progenitor populations of the mammary epithelium is likely to underpin the heterogeneity that characterizes breast cancer.

scholarly journals The Making of Hematopoiesis: Developmental Ancestry and Environmental Nurture

2018 ◽  
Vol 19 (7) ◽  
pp. 2122 ◽  
Author(s):  
Geoffrey Brown ◽  
Rhodri Ceredig ◽  
Panagiotis Tsapogas
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Hematopoietic Stem ◽  
Fate Determination ◽  
Intermediate Progenitors ◽  
Lineage Tree ◽  
Stem And Progenitor Cells ◽  
The Many

Evidence from studies of the behaviour of stem and progenitor cells and of the influence of cytokines on their fate determination, has recently led to a revised view of the process by which hematopoietic stem cells and their progeny give rise to the many different types of blood and immune cells. The new scenario abandons the classical view of a rigidly demarcated lineage tree and replaces it with a much more continuum-like view of the spectrum of fate options open to hematopoietic stem cells and their progeny. This is in contrast to previous lineage diagrams, which envisaged stem cells progressing stepwise through a series of fairly-precisely described intermediate progenitors in order to close down alternative developmental options. Instead, stem and progenitor cells retain some capacity to step sideways and adopt alternative, closely related, fates, even after they have “made a lineage choice.” The stem and progenitor cells are more inherently versatile than previously thought and perhaps sensitive to lineage guidance by environmental cues. Here we examine the evidence that supports these views and reconsider the meaning of cell lineages in the context of a continuum model of stem cell fate determination and environmental modulation.

scholarly journals Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells

2015 ◽  
Vol 308 (7) ◽  
pp. G573-G578 ◽  
Author(s):  
Laurent Dollé ◽  
Luke Boulter ◽  
Isabelle A. Leclercq ◽  
Leo A. van Grunsven
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Cell Phenotype ◽  
Tissue Cell ◽  
Aldh Activity ◽  
Fluorescent Substrate ◽  
Metabolic Role ◽  
Stem And Progenitor Cells ◽  
Active Research

High aldehyde dehydrogenase (ALDH) activity is a feature of stem cells from normal and cancerous tissues and a reliable universal marker used to isolate them. There are numerous ALDH isoforms with preferred substrate specificity variably expressed depending on tissue, cell type, and organelle and cell status. On the other hand, a given substrate may be metabolized by several enzyme isoforms. Currently ALDH activity is evidenced by using Aldefluor, a fluorescent substrate likely to be metabolized by numerous ALDH isoforms. Therefore, isolation techniques based on ALDH activity detection select a heterogeneous population of stem or progenitor cells. Despite active research in the field, the precise role(s) of different ALDH isoforms in stem cells remains enigmatic. Understanding the metabolic role of different ALDH isoform in the control of stem cell phenotype and cell fate during development, tissue homeostasis, or repair, as well as carcinogenesis, should open perspectives to significant discoveries in tissue biology. In this perspective, novel ALDH substrates are being developed. Here we describe how new substrates could be instrumental for better isolation of cell population with stemness potential and for defining hierarchy of cell populations in tissue. Finally, we speculate on other potential applications.

scholarly journals Stem Cells and Cellular Origins of Mammary Gland: Updates in Rationale, Controversies, and Cancer Relevance

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jiaojiao Zhou ◽  
Qishan Chen ◽  
Yiheng Zou ◽  
Shu Zheng ◽  
Yiding Chen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Cell Biology ◽  
Mammary Epithelium ◽  
Lineage Tracing ◽  
Basal Cells ◽  
Mammary Stem Cells ◽  
Mammary Stem ◽  
Cell Niche

Evidences have supported the pivotal roles of stem cells in mammary gland development. Many molecular markers have been identified to characterize mammary stem cells. Cellular fate mapping of mammary stem cells by lineage tracing has put unprecedented insights into the mammary stem cell biology, which identified two subtypes of mammary stem cells, including unipotent and multipotent, which specifically differentiate to luminal or basal cells. The emerging single-cell sequencing profiles have given a more comprehensive understanding on the cellular hierarchy and lineage signatures of mammary epithelium. Besides, the stem cell niche worked as an essential regulator in sustaining the functions of mammary stem cells. In this review, we provide an overview of the characteristics of mammary stem cells. The cellular origins of mammary gland are discussed to understand the stem cell heterogeneity and their diverse differentiations. Importantly, current studies suggested that the breast cancer stem cells may originate from the mammary stem cells after specific mutations, indicating their close relationships. Here, we also outline the recent advances and controversies in the cancer relevance of mammary stem cells.

scholarly journals The inhibition of KDM2B promotes the differentiation of basal-like breast cancer cells via the posttranslational destabilization of SLUG

2020 ◽  
Author(s):  
Elia Aguado Fraile ◽  
Evangelia Chavdoula ◽  
Georgios I. Laliotis ◽  
Vollter Anastas ◽  
Oksana Serebrennikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Progenitor Cells ◽  
Breast Cancer Stem Cells ◽  
Cells In Culture ◽  
Mammary Stem ◽  
Stem And Progenitor Cells ◽  
Basal Like Breast Cancer ◽  
Jmjc Domain

ABSTRACTKDM2B is a JmjC domain H3K36me2/H3K36me1 demethylase, which immortalizes cells in culture and contributes to the biology of both embryonic and adult stem and progenitor cells. It also functions as an oncogene that contributes to the self-renewal of breast cancer stem cells by regulating polycomb complexes. Here we show that the silencing of KDM2B results in the downregulation of SNAI2 (SLUG), SNAI1 (SNAIL) and SOX9, which also contribute to the biology of mammary stem and progenitor cells. The downregulation of these molecules is posttranscriptional and in the case of the SNAI2-encoded SLUG, it is due to calpain-dependent proteolytic degradation. Mechanistically, the latter depends on the activation of calpastatin-sensitive classical calpain(s) and on the phosphorylation-dependent inhibition of GSK3 via paracrine mechanisms. GSK3 inhibition sensitizes its target SLUG to classical calpains, which are activated by Ca2+ influx and calpastatin downregulation. The degradation of SLUG, induced by the KDM2B knockdown, promotes the differentiation of breast cancer stem cells in culture and reveals an unexpected mechanism of stem cell regulation by a histone demethylase.

scholarly journals Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

Organogenesis ◽  
2014 ◽  
Vol 10 (4) ◽  
pp. 365-377 ◽  
Author(s):  
Leonardo D’Aiuto ◽  
Yun Zhi ◽  
Dhanjit Kumar Das ◽  
Madeleine R Wilcox ◽  
Jon W Johnson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Large Scale ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Human Ipsc

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

scholarly journals 3D Differentiation Of Mammosphere Derived Macaca fascicularis’s Mammary Stem Cells

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Silmi Mariya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Cell Population ◽  
Mammary Stem Cell ◽  
Stem Cell Population ◽  
Stem Cell Markers ◽  
Mammary Stem Cells ◽  
Surgical Biopsy ◽  
Mammary Stem

The mammary gland contains adult stem cells that are capable of self-renewal.  This population plays an important role in the development of mammary gland and breast cancer pathogenesis. The studies of mammary stem cells are limited due to the difficulty to acquire and expand adult stem cell population in an undifferentiated state. In this study, we developed mammosphere cultures of nulliparous cynomolgus monkeys (Macaca fascicularis; Mf) as a culture system to enrich mammary stem cells. This species has similarity of mammary gland structure as humans including anatomy, developmental stages, and lobule profile of mammary gland. The use of stem cells from primate animals is essential to bridge the knowledge gaps resulting from stem cell research using rodents for clinical trials in human. Small samples of mammary tissues were collected by surgical biopsy; cells were cultured as monolayer and cryopreserved. Cryopreserved cells were cultured into mammospheres, and the expression of markers for mammary stem cells was evaluated using qPCR. Cells were further differentiated with 3D approaches to evaluate morphology and organoid budding. The study showed that mammosphere culture resulted in an increase in the expression of mammary stem cell markers with each passage. The 3D differentiation in matrigel allowed for organoid formation. Mammary gland stem cells have been successfully differentiated which characterized by CSN2 marker expression and differentiation regulators marker STAT5 and GATA3. The results indicate that mammospheres can be successfully developed derived from breast tissue of nulliparous Mf collected via surgical biopsy. As the mammosphere allows for enrichment of mammary stem cell population, the findings also suggest that a 3-dimensional system is efficient as in-vitro model to study mammary stem cells and a useful system to study mammary differentiation in regards to cancer prevention.

scholarly journals Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development

2020 ◽  
Author(s):  
Alexandr Samocha ◽  
Hanna M. Doh ◽  
Vaishnavi Sitarama ◽  
Quy H. Nguyen ◽  
Oghenekevwe Gbenedio ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Gene Signature ◽  
Mammary Epithelial ◽  
Fine Tuning ◽  
Basal Cells ◽  
Stem And Progenitor Cells

SummaryDuring puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically and in vitro, Rasgrp1 perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However, in vivo, Rasgrp1 perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity. Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.

Sign in / Sign up

Export Citation Format

Share Document