scholarly journals Division-independent differentiation mandates proliferative competition among stem cells

2018 ◽  
Vol 115 (14) ◽  
pp. E3182-E3191 ◽  
Author(s):  
Amy Reilein ◽  
David Melamed ◽  
Simon Tavaré ◽  
Daniel Kalderon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Lineage ◽  
Proliferation Rate ◽  
Genetic Changes ◽  
Stem Cell Lineage ◽  
Stem Cell Division ◽  
Follicle Stem Cells ◽  
The Impact

Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space. We considered alternative mechanisms underlying population asymmetry and used quantitative modeling to predict starkly different consequences of altering proliferation rate: A variant, faster proliferating mutant stem cell should compete better only when stem cell division and differentiation are independent processes. For most types of stem cells, it has not been possible to ascertain experimentally whether division and differentiation are coupled. However, Drosophila follicle stem cells (FSCs) provided a favorable system with which to investigate population asymmetry mechanisms and also for measuring the impact of altered proliferation on competition. We found from detailed cell lineage studies that division and differentiation of an individual FSC are not coupled. We also found that FSC representation, reflecting maintenance and amplification, was highly responsive to genetic changes that altered only the rate of FSC proliferation. The FSC paradigm therefore provides definitive experimental evidence for the general principle that relative proliferation rate will always be a major determinant of competition among stem cells specifically when stem cell division and differentiation are independent.

scholarly journals Division-independent differentiation mandates proliferative competition among stem cells

2017 ◽  
Author(s):  
Amy Reilein ◽  
David Melamed ◽  
Simon Tavaré ◽  
Daniel Kalderon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Experimental Evidence ◽  
Adult Stem Cells ◽  
Proliferation Rate ◽  
Quantitative Modeling ◽  
Stem Cell Division ◽  
Follicle Stem Cells ◽  
The Impact

SUMMARYCancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem lineage (1, 2). It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate stem cell proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetric division outcomes or by population asymmetry strategies, in which individual stem cell lineages necessarily compete for niche space. We considered alternative mechanisms underlying population asymmetry and used quantitative modeling to predict starkly different consequences of altering proliferation rate: a variant, faster-proliferating mutant stem cell should compete better only when stem cell division and differentiation are independent processes. For most types of stem cell it has not been possible to ascertain experimentally whether division and differentiation are coupled. However, Drosophila Follicle Stem Cells (FSCs) provided a favorable model system to investigate population asymmetry mechanisms and also for measuring the impact of altered proliferation on competition. We found from detailed cell lineage studies that FSC division and FSC differentiation are not coupled. We also found that FSC representation, reflecting maintenance and amplification, was highly responsive to genetic changes that altered only the rate of FSC proliferation. The FSC paradigm therefore provides definitive experimental evidence for the general principle that relative proliferation rate will always be a major determinant of competition among stem cells specifically when stem cell division and differentiation are independent.SIGNIFICANCEAdult stem cells support tissue maintenance throughout life but they also can be cells of origin for cancer, allowing clonal expansion and long-term maintenance of the first oncogenic mutations. We considered how a mutation that increases the proliferation rate of a stem cell would affect the probability of its competitive survival and amplification for different potential organizations of stem cells. Quantitative modeling showed that the key characteristic predicting the impact of relative proliferation rate on competition is whether differentiation of a stem cell is coupled to its division. We then used Drosophila Follicle Stem Cells to provide definitive experimental evidence for the general prediction that relative proliferation rates dictate stem cell competition specifically for stem cells that exhibit division-independent differentiation.

scholarly journals Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
David Melamed ◽  
Daniel Kalderon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Wnt Pathway ◽  
Adult Stem Cell ◽  
Follicle Cells ◽  
Pathway Activity ◽  
Stem Cell Division ◽  
Follicle Stem Cells ◽  
Stat Pathway

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between stem cell division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) by spatially-restricted niche signals. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. We show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC domain, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. Wnt pathway activity declines from the anterior, promotes anterior FSC locations and EC production, and opposes FC production. The pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs and FCs at either end of opposing signaling gradients, and impose a pattern of proliferation that matches derivative production.

The Neural Stem Cell Lineage Reveals Novel Relationships Among Spermatogonial Germ Stem Cells and Other Pluripotent Stem Cells

2014 ◽  
Vol 23 (7) ◽  
pp. 767-778 ◽  
Author(s):  
Anouk-Martine Teichert ◽  
Schreiber Pereira ◽  
Brenda Coles ◽  
Radha Chaddah ◽  
Susan Runciman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cell Lineage ◽  
Stem Cell Lineage

scholarly journals Emerging mechanisms of asymmetric stem cell division

2018 ◽  
Vol 217 (11) ◽  
pp. 3785-3795 ◽  
Author(s):  
Zsolt G. Venkei ◽  
Yukiko M. Yamashita
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Binary Outcomes ◽  
Cellular Mechanisms ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Dividing Cells ◽  
Stem Cell Division

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

scholarly journals Planarian stem cells sense the identity of the missing pharynx to launch its targeted regeneration

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Tisha E Bohr ◽  
Divya A Shiroor ◽  
Carolyn E Adler
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Types ◽  
Erk Signaling ◽  
Stem Cell Population ◽  
Cell Responses ◽  
Stem Cell Division ◽  
Tissue Production ◽  
Single Organ

In order to regenerate tissues successfully, stem cells must detect injuries and restore missing cell types through largely unknown mechanisms. Planarian flatworms have an extensive stem cell population responsible for regenerating any organ after amputation. Here, we compare planarian stem cell responses to different injuries by either amputation of a single organ, the pharynx, or removal of tissues from other organs by decapitation. We find that planarian stem cells adopt distinct behaviors depending on what tissue is missing to target progenitor and tissue production towards missing tissues. Loss of non-pharyngeal tissues only increases non-pharyngeal progenitors, while pharynx removal selectively triggers division and expansion of pharynx progenitors. By pharmacologically inhibiting either mitosis or activation of the MAP kinase ERK, we identify a narrow window of time during which stem cell division and ERK signaling produces pharynx progenitors necessary for regeneration. These results indicate that planarian stem cells can tailor their output to match the regenerative needs of the animal.

scholarly journals Stem Cells, Diet, and Physiology

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Daniela Drummond-Barbosa
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Regulation ◽  
Stem Cell Lineage ◽  
Sensor Control ◽  
Nutrient Signaling ◽  
Multicellular Organisms

Abstract Nutrient availability, stresses, and aging affect tissue stem cells in multicellular organisms; yet, the underlying physiological mechanisms in vivo remains largely unexplored. Dr. Drummond-Barbosa pioneered using Drosophila to study the physiology of tissue stem cell regulation. Her laboratory played a major role in delineating how diet, brain insulin-like peptides, and the TOR nutrient sensor control the germline stem cell (GSC) lineage. They also discovered that adipocyte-specific disruption of amino acid transport, other nutrient signaling, and metabolic pathways causes distinct germline phenotypes. They also showed that nuclear receptors act in multiple tissues to affect the GSC lineage through direct and indirect mechanisms. More recently, her group has been exploring how other physiological stresses affect the GSC lineage. Her group’s studies point to extensive communication between the brain, adipocytes, hepatocyte-like cells, and the germline, and underscore the complexity of the physiological network that modulates stem cell lineage behavior.

scholarly journals Roles of Melatonin in Goat Hair Follicle Stem Cell Proliferation and Pluripotency Through Regulating the Wnt Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Weidong Zhang ◽  
Niu Wang ◽  
Tongtong Zhang ◽  
Meng Wang ◽  
Wei Ge ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Wnt Signaling Pathway ◽  
Hematopoietic Progenitor Cell ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells ◽  
The Impact

Emerging studies show that melatonin promotes cashmere development through hypodermic implantation. However, the impact and underlying mechanisms are currently unknown. In vitro study has previously demonstrated that melatonin induces cashmere growth by regulating the proliferation of goat secondary hair follicle stem cells (gsHFSCs), but there is limited information concerning the effects of melatonin on cell pluripotency. It is also known that Wnt signaling may actively participate in regulating cell proliferation and stem cell pluripotency. Therefore, in the current investigation, goat hair follicle stem cells were exposed to multiple concentrations of melatonin and different culture times to reveal the relationship between melatonin and the activation of Wnt signaling. A proportionally high Catenin beta-1 (CTNNB1) response was induced by 500 ng/L of melatonin, but it was then suppressed with the dosages over 1,000 ng/L. Greater amounts of CTNNB1 entered the cell nuclei by extending the exposure time to 72 h, which activated transcription factor 4/lymphoid enhancer-binding factor 1 and promoted the expression of the proliferation-related genes C-MYC, C-JUN, and CYCLIND1. Moreover, nuclear receptor ROR-alpha (RORα) and bone morphogenetic protein 4 (BMP4) were employed to analyze the underlying mechanism. RORα presented a sluggish concentration/time-dependent rise, but BMP4 was increased dramatically by melatonin exposure, which revealed that melatonin might participate in regulating the pluripotency of hair follicle stem cells. Interestingly, NOGGIN, which is a BMP antagonist and highly relevant to cell stemness, was also stimulated by melatonin. These findings demonstrated that melatonin exposure and/or NOGGIN overexpression in hair follicle stem cells might promote the expression of pluripotency markers Homeobox protein NANOG, Organic cation/carnitine transporter 4, and Hematopoietic progenitor cell antigen CD34. Our findings here provided a comprehensive view of Wnt signaling in melatonin stimulated cells and melatonin mediated stemness of gsHFSCs by regulating NOGGIN, which demonstrates a regulatory mechanism of melatonin enhancement on the growth of cashmere.

scholarly journals Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division

2021 ◽  
Vol 118 (13) ◽  
pp. e2006786118
Author(s):  
Justin Sardi ◽  
Muhammed Burak Bener ◽  
Taylor Simao ◽  
Abigail E. Descoteaux ◽  
Boris M. Slepchenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Daughter Cell ◽  
High Sensitivity ◽  
Bmp Signaling ◽  
Nuclear Pore ◽  
Germline Stem Cells ◽  
Stem Cell Division ◽  
Asymmetric Partitioning

Stem cells divide asymmetrically to generate a stem cell and a differentiating daughter cell. Yet, it remains poorly understood how a stem cell and a differentiating daughter cell can receive distinct levels of niche signal and thus acquire different cell fates (self-renewal versus differentiation), despite being adjacent to each other and thus seemingly exposed to similar levels of niche signaling. In the Drosophila ovary, germline stem cells (GSCs) are maintained by short range bone morphogenetic protein (BMP) signaling; the BMP ligands activate a receptor that phosphorylates the downstream molecule mothers against decapentaplegic (Mad). Phosphorylated Mad (pMad) accumulates in the GSC nucleus and activates the stem cell transcription program. Here, we demonstrate that pMad is highly concentrated in the nucleus of the GSC, while it quickly decreases in the nucleus of the differentiating daughter cell, the precystoblast (preCB), before the completion of cytokinesis. We show that a known Mad phosphatase, Dullard (Dd), is required for the asymmetric partitioning of pMad. Our mathematical modeling recapitulates the high sensitivity of the ratio of pMad levels to the Mad phosphatase activity and explains how the asymmetry arises in a shared cytoplasm. Together, these studies reveal a mechanism for breaking the symmetry of daughter cells during asymmetric stem cell division.

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