scholarly journals Stem cell niche signals Wnt, Hedgehog, and Notch distinctively regulate Drosophila follicle precursor cell differentiation

2017 ◽  
Author(s):  
Wei Dai ◽  
Amy Peterson ◽  
Thomas Kenney ◽  
Denise J. Montell

AbstractAdult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. Signals within the stem cell niche maintain the undifferentiated state. However it is unclear whether or how niche signals might also coordinate fate decisions within the progenitor pool. Here we use quantitative microscopy to elucidate distinct roles for Wnt, Hedgehog (Hh), and Notch signalling in progenitor development in the Drosophila ovary. Follicle stem cells (FSCs) self-renew and produce precursors whose progeny adopt distinct polar, stalk, and main body cell fates. We show that a steep gradient of Wnt signalling maintains a multipotent state in proximally located progenitor cells by inhibiting expression of the cell fate determinant Eyes Absent (Eya). A shallower gradient of Hh signalling controls the proliferation to differentiation transition. The combination of Notch and Wnt signalling specifies polar cells. These findings reveal a mechanism by which multiple niche signals coordinate cell fate diversification of progenitor cells.

2018 ◽  
Vol 20 (1) ◽  
pp. 21-47 ◽  
Author(s):  
Christopher M. Madl ◽  
Sarah C. Heilshorn

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell–cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.


2011 ◽  
pp. 35-55 ◽  
Author(s):  
Yoshiko Matsumoto ◽  
Hiroko Iwasaki ◽  
Toshio Suda

2006 ◽  
Vol 290 (2) ◽  
pp. G189-G193 ◽  
Author(s):  
Neil D. Theise

This essay will address areas of liver stem/progenitor cell studies in which consensus has emerged and in which controversy still prevails over consensus, but it will also highlight important themes that inevitably should be a focus of liver stem/progenitor cell investigations in coming years. Thus concepts regarding cell plasticity, the existence of a physiological/anatomic stem cell niche, and whether intrahepatic liver stem/progenitor cells comprise true stem cells or progenitor cells (or both) will be approached in some detail.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zijian Xu ◽  
Wenjie Wang ◽  
Kaiju Jiang ◽  
Zhou Yu ◽  
Huanwei Huang ◽  
...  

Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation.


2009 ◽  
Vol 29 (22) ◽  
pp. 6086-6096 ◽  
Author(s):  
Hongjuan Gao ◽  
Xiaorong Wu ◽  
Nancy Fossett

ABSTRACT Studies using Drosophila melanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in third-instar lymph gland prohemocytes and downregulated in a subpopulation of differentiating blood cells. Genetic analyses indicated that U-shaped maintains the prohemocyte population by blocking differentiation. In addition, activated STAT directly regulated ush expression as evidenced by results from loss- and gain-of-function studies and from analyses of the u-shaped hematopoietic cis-regulatory module. Collectively, these findings identify U-shaped as a downstream effector of the posterior signaling center, establishing a novel link between the stem cell niche and the intrinsic regulation of potency and differentiation. Given the functional conservation of Friend of GATA proteins and the role that GATA factors play during cell fate choice, these factors may regulate essential functions of vertebrate hematopoietic stem cells, including processing signals from the stem cell niche.


2011 ◽  
Vol 11 ◽  
pp. 1762-1769 ◽  
Author(s):  
A. N. Schüring ◽  
J. Braun ◽  
S. Wüllner ◽  
L. Kiesel ◽  
M. Götte

Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERβ, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies.Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERβand PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression.Results. Expression of ERαand ERβwas downregulated by 64% and 89%, respectively ( and ). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern.Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERαand ERβ, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche.


2020 ◽  
Author(s):  
Madalina-Gabriela Barbu ◽  
Andreea-Elena Boboc ◽  
Lidia Filip ◽  
Oana-Larisa Bugnar ◽  
Dragos Cretoiu ◽  
...  

Stem cells are defined as undifferentiated cells that are able to unlimitedly renew themselves within controlled conditions and to differentiate into a multitude of mature cell types. Skeletal muscle stem cells, represented predominantly by satellite cells, show a variable capability of self-renewal and myogenic differentiation. They were found to be involved not only in the growth of myofibers during neonatal and juvenile life but also in the regeneration of skeletal muscles after an injury. The microenvironment in which stem cells are nourished and maintained dormant preceding division and differentiation is known as “niche.” The niche consists of myofibers, which are believed to modulate the active/inactive state of the stem cells, extracellular matrix, neural networks, blood vessels, and a multitude of soluble molecules. It was observed that changes in the composition of the niche have an impact on the stem cell functions and hierarchy. Furthermore, it seems that its layout is variable throughout the entire life, translating into a decrease in the regenerative capacity of satellite cells in aged tissues. The scope of this chapter is to provide a detailed view of the changes that occur in the skeletal stem cell niche during life and to analyze their implications on tissue regeneration. Future studies should focus on developing new therapeutic tools for diseases involving muscle atrophy.


Open Biology ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. 170140 ◽  
Author(s):  
Kate M. Mills ◽  
James L. A. Szczerkowski ◽  
Shukry J. Habib

Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells. We also highlight recent progress in molecular visualization that has allowed for the monitoring of Wnt signalling within the stem cell compartment and new approaches to recapitulate this niche signalling in vitro . Indeed, new technologies that present Wnt in a localized manner and mimic the three-dimensional microenvironment of stem cells will advance our understanding of Wnt signalling in the stem cell niche. These advances will expand current horizons to exploit Wnt ligands in the rapidly evolving fields of tissue engineering and regenerative medicine.


2015 ◽  
Author(s):  
Adam L MacLean ◽  
Paul Kirk ◽  
Michael PH Stumpf

Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain "stemness" through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell--niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly) high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell--cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche -- and hence of the stem cell pool in the niche -- depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.


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