scholarly journals GABA-A signaling maintains melanocyte stem cell quiescence in larval zebrafish

2019 ◽  
Author(s):  
James R. Allen ◽  
James B. Skeath ◽  
Stephen L. Johnson
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Tissue Homeostasis ◽  
Gaba A ◽  
Larval Zebrafish ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Melanocyte Stem Cells ◽  
Necessary And Sufficient

AbstractAdult stem cells (ASCs) contribute to long-term homeostasis and regeneration of many adult tissues. Some ASCs proliferate continuously, others remain quiescent awaiting activation. To identify pathways that regulate ASC quiescence and tissue homeostasis, we study melanocyte stem cells (MSCs) that drive vertebrate pigmentation. In larval zebrafish, MSCs are quiescent, but can be recruited to regenerate the larval pigment pattern following melanocyte ablation. Through pharmacological experiments, we found that inhibition of GABA-A receptor function, specifically the GABA-A rho subtype, induces excessive melanocyte production in larval zebrafish. Conversely, pharmacological activation of GABA-A inhibited melanocyte regeneration. We used CRISPR to generate two mutant alleles of gabrr1, a subtype of GABA-A. Both alleles exhibited robust melanocyte overproduction, while conditional overexpression of gabrr1 inhibited larval melanocyte regeneration. Our data suggest that gabrr1 signaling is necessary and sufficient to maintain MSC quiescence and prevent excessive pigmentation of the larval zebrafish.

scholarly journals Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Isabelle Maria Blomfield ◽  
Brenda Rocamonde ◽  
Maria del Mar Masdeu ◽  
Eskeatnaf Mulugeta ◽  
Stefania Vaga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Activation ◽  
Id Proteins ◽  
Stem Cell Quiescence ◽  
Activation Factor ◽  
Abnormal Accumulation ◽  
Inhibitor Of Dna Binding

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors.

scholarly journals Maintenance of Melanocyte Stem Cell Quiescence by GABA-A Signaling in Larval Zebrafish

Genetics ◽  
2019 ◽  
Vol 213 (2) ◽  
pp. 555-566 ◽  
Author(s):  
James R. Allen ◽  
James B. Skeath ◽  
Stephen L. Johnson
Keyword(s):  
Stem Cell ◽  
Gaba A ◽  
Larval Zebrafish ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Melanocyte Stem Cell

scholarly journals Stem cell quiescence: the challenging path to activation

Development ◽  
2021 ◽  
Vol 148 (3) ◽  
pp. dev165084
Author(s):  
Noelia Urbán ◽  
Tom H. Cheung
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Adult Stem Cells ◽  
Quiescent State ◽  
Regenerative Capacity ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Technical Advances ◽  
A Cell ◽  
Unique Ability

ABSTRACTQuiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity. Quiescence has long been viewed as an inactive state but recent studies have shown that it is in fact an actively regulated process and that adult stem cells are highly reactive to extrinsic stimuli. This has fuelled hopes of boosting the reactivation potential of adult stem cells to improve tissue function during ageing. In this Review, we provide a perspective of the quiescent state and discuss how quiescent adult stem cells transition into the cell cycle. We also discuss current challenges in the field, highlighting recent technical advances that could help overcome some of these challenges.

scholarly journals Human Adult Stem Cells Maintain a Constant Phenotype Profile Irrespective of Their Origin, Basal Media, and Long Term Cultures

2015 ◽  
Vol 2015 ◽  
pp. 1-29 ◽  
Author(s):  
Indumathi Somasundaram ◽  
Rashmi Mishra ◽  
Harikrishnan Radhakrishnan ◽  
Rajkumar Sankaran ◽  
Venkata Naga Srikanth Garikipati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Expression Profiles ◽  
Subcutaneous Fat ◽  
Adult Stem Cell ◽  
Phenotypic Marker ◽  
Human Adult ◽  
Cell Based Therapy ◽  
Basal Media

The study aims to identify the phenotypic marker expressions of different human adult stem cells derived from, namely, bone marrow, subcutaneous fat, and omentum fat, cultured in different media, namely, DMEM-Low Glucose, Alpha-MEM, DMEM-F12 and DMEM-KO and under long term culture conditions (>P20). We characterized immunophenotype by using various hematopoietic, mesenchymal, endothelial markers, and cell adhesion molecules in the long term cultures (Passages-P1, P3, P5, P9, P12, P15, and P20.) Interestingly, data revealed similar marker expression profiles irrespective of source, basal media, and extensive culturing. This demonstrates that all adult stem cell sources mentioned in this study share similar phenotypic marker and all media seem appropriate for culturing these sources. However, a disparity was observed in the markers such as CD49d, CD54, CD117, CD29, and CD106, thereby warranting further research on these markers. Besides the aforesaid objective, it is understood from the study that immunophenotyping acts as a valuable tool to identify inherent property of each cell, thereby leading to a valuable cell based therapy.

scholarly journals “Opening” The Mesenchymal Stem Cell Tool Box

2009 ◽  
Vol 03 (03) ◽  
pp. 240-249 ◽  
Author(s):  
Fares Zeidán-Chuliá ◽  
Mami Noda
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Current Status ◽  
Tooth Replacement ◽  
Cell Based Therapy ◽  
Adult Mesenchymal Stem Cells ◽  
Wide Potential ◽  
New Strategies

ABSTRACTAdult mesenchymal stem cells (MSCs) are adherent stromal cells able to self-renew and differentiate into a wide variety of cells and tissues. MSCs can be obtained from distinct tissue sources and have turned out to be successfully manipulated in vitro. As adult stem cells, MSCs are less tumorigenic than their embryonic correlatives and posses another unique characteristic which is their almost null immunogenicity. Moreover, these cells seem to be immunosuppressive in vitro. These facts together with others became MSCs a promising subject of study for future approaches in bioengineering and cell-based therapy. On the other hand, new strategies to achieve long-term integration as well as efficient differentiation of these cells at the area of the lesion are still challenging, and the signalling pathways ruling these processes are not completely well characterized. In this review, we are going summarize the general landscape and current status of the MSC tool as well as their wide potential in tissue engineering, from neuronal to tooth replacement. Highlights and pitfalls for further clinical applications will be discussed. (Eur J Dent 2009;3:240-249)

scholarly journals TIMP-1 deficiency subverts cell-cycle dynamics in murine long-term HSCs

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6479-6488 ◽  
Author(s):  
Lara Rossi ◽  
Aysegul V. Ergen ◽  
Margaret A. Goodell
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Distribution ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Homeostatic Regulation ◽  
Intrinsic Cues ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Cell Cycle Dynamics

Abstract In addition to the well-recognized role in extracellular matrix remodeling, the tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be involved in the regulation of numerous biologic functions, including cell proliferation and survival. We therefore hypothesized that TIMP-1 might be involved in the homeostatic regulation of HSCs, whose biologic behavior is the synthesis of both microenvironmental and intrinsic cues. We found that TIMP-1−/− mice have decreased BM cellularity and, consistent with this finding, TIMP-1−/− HSCs display reduced capability of long-term repopulation. Interestingly, the cell cycle distribution of TIMP-1−/− stem cells appears distorted, with a dysregulation at the level of the G1 phase. TIMP-1−/− HSCs also display increased levels of p57, p21, and p53, suggesting that TIMP-1 could be intrinsically involved in the regulation of HSC cycling dynamics. Of note, TIMP-1−/− HSCs present decreased levels of CD44 glycoprotein, whose expression has been proven to be controlled by p53, the master regulator of the G1/S transition. Our findings establish a role for TIMP-1 in regulating HSC function, suggesting a novel mechanism presiding over stem cell quiescence in the framework of the BM milieu.

scholarly journals Msi RNA-binding proteins control reserve intestinal stem cell quiescence

2016 ◽  
Vol 215 (3) ◽  
pp. 401-413 ◽  
Author(s):  
Maryam Yousefi ◽  
Ning Li ◽  
Angela Nakauka-Ddamba ◽  
Shan Wang ◽  
Kimberly Davidow ◽  
...  
Keyword(s):  
Stem Cell ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intestinal Stem Cell ◽  
Stem Cell Population ◽  
Cell Compartment ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Necessary And Sufficient

Regeneration of the intestinal epithelium is driven by multiple intestinal stem cell (ISC) types, including an active, radiosensitive Wnthigh ISC that fuels turnover during homeostasis and a reserve, radioresistant Wntlow/off ISC capable of generating active Wnthigh ISCs. We examined the role of the Msi family of oncoproteins in the ISC compartment. We demonstrated that Msi proteins are dispensable for normal homeostasis and self-renewal of the active ISC, despite their being highly expressed in these cells. In contrast, Msi proteins are required specifically for activation of reserve ISCs, where Msi activity is both necessary and sufficient to drive exit from quiescence and entry into the cell cycle. Ablation of Msi activity in reserve ISCs rendered the epithelium unable to regenerate in response to injury that ablates the active stem cell compartment. These findings delineate a molecular mechanism governing reserve ISC quiescence and demonstrate a necessity for the activity of this rare stem cell population in intestinal regeneration.

scholarly journals mRNP granule proteins Fmrp and Dcp1a differentially regulate mRNP complexes to contribute to control of muscle stem cell quiescence

2021 ◽  
Author(s):  
Nainita Roy ◽  
Swetha Sundar ◽  
Malini Pillai ◽  
Farah Patell-Socha ◽  
Sravya Ganesh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Sectional Area ◽  
Cross Sectional ◽  
Muscle Stem Cell ◽  
Translational Repressor ◽  
Stem Cell Quiescence ◽  
Culture Model ◽  
Cell Quiescence ◽  
Granule Proteins

Abstract Background: During skeletal muscle regeneration, satellite stem cells use distinct pathways to repair damaged myofibers or to self-renew by returning to quiescence. Cellular/mitotic quiescence employs mechanisms that promote a poised or primed state, including altered RNA turnover and translational repression. Here, we investigate the role of mRNP granule proteins Fragile X Mental Retardation Protein (Fmrp) and Decapping protein 1a (Dcp1a) in muscle stem cell quiescence and differentiation.Methods: Using isolated single muscle fibers from adult mice, we established differential enrichment of mRNP granule proteins including Fmrp and Dcp1a in muscle stem cells vs. myofibers. We investigated muscle tissue homeostasis in adult Fmr1-/- mice, analyzing myofiber cross-sectional area in vivo and satellite cell proliferation ex vivo. We explored the molecular mechanisms of Dcp1a and Fmrp function in quiescence, proliferation and differentiation in a C2C12 culture model. Here, we used polysome profiling, imaging and RNA/protein expression analysis to establish the abundance and assembly status of mRNP granule proteins in different cellular states, and the phenotype of knockdown cells.Results: Quiescent muscle satellite cells are enriched for puncta containing the translational repressor Fmrp, but not the mRNA decay factor Dcp1a. MuSC isolated from Fmr1-/- mice exhibit defective proliferation and mature myofibers show reduced cross-sectional area, suggesting a role for Fmrp in muscle homeostasis. Expression and organization of Fmrp and Dcp1a varies during primary MuSC activation on myofibers, with Fmrp puncta prominent in quiescence, but Dcp1a puncta appearing during activation/proliferation. This reciprocal expression of Fmrp and Dcp1a puncta is recapitulated in a C2C12 culture model of quiescence and activation: consistent with its role as a translational repressor, Fmrp is enriched in non-translating mRNP complexes abundant in quiescent myoblasts; Dcp1a puncta are lost in quiescence, suggesting stabilized and repressed transcripts. The function of each protein differs during proliferation; whereas Fmrp knockdown led to decreased proliferation and lower cyclin expression, Dcp1a knockdown led to increased cell proliferation and higher cyclin expression. However, knockdown of either Fmrp or Dcp1a led to compromised differentiation. We also observed cross-regulation of decay versus storage mRNP granules; knockdown of Fmrp enhances accumulation of Dcp1a puncta, whereas knockdown of Dcp1a leads to increased Fmrp in puncta.Conclusions: Taken together, our results provide evidence that the balance of mRNA turnover versus utilization is specific for distinct cellular states.

scholarly journals mRNP Granule Proteins Fmrp and Dcp1a Differentially Regulate Muscle Stem Cell Quiescence via Reciprocally Regulating mRNP Complexes

2020 ◽  
Author(s):  
Nainita Roy ◽  
Malini Pillai ◽  
Farah Patell-Socha ◽  
Swetha Sundar ◽  
Sravya Ganesh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Sectional Area ◽  
Cross Sectional ◽  
Muscle Stem Cell ◽  
Translational Repressor ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Granule Proteins

Abstract Background: During skeletal muscle regeneration, satellite stem cells use distinct pathways to repair damaged myofibers or to self-renew by returning to quiescence. Cellular/mitotic quiescence employs mechanisms that promote a poised or primed state, including altered RNA turnover and translational repression. Here, we investigate the role of mRNP granule proteins Fragile X Mental Retardation Protein (Fmrp) and Decapping protein 1a (Dcp1a) in muscle stem cell quiescence and differentiation.Methods: Using isolated single muscle fibers from adult mice, we established differential enrichment of mRNP granule proteins including Fmrp and Dcp1a in muscle stem cells vs. myofibers. We investigated muscle tissue homeostasis in adult Fmr1-/- mice, analyzing myofiber cross-sectional area in vivo and satellite cell proliferation ex vivo. We explored the molecular mechanisms of Dcp1a and Fmrp function in quiescence, proliferation and differentiation in a C2C12 culture model. Here, we used polysome profiling, imaging and RNA/protein expression analysis to establish the abundance and assembly status of mRNP granule proteins in different cellular states, and the phenotype of knockdown cells.Results: Quiescent muscle satellite cells are enriched for puncta containing the translational repressor Fmrp, but not the mRNA decay factor Dcp1a. MuSC isolated from Fmr1-/- mice exhibit defective proliferation and mature myofibers show reduced cross-sectional area, suggesting a role for Fmrp in muscle homeostasis. Expression and organization of Fmrp and Dcp1a varies between different cell states in culture. Consistent with its role as a translational repressor, Fmrp is enriched in non-translating mRNP complexes abundant in quiescent myoblasts; Dcp1a puncta are lost in quiescence, suggesting stabilized and repressed transcripts. The function of each protein differs during proliferation; whereas Fmrp knockdown led to decreased proliferation and lower cyclin expression, Dcp1a knockdown led to increased cell proliferation and higher cyclin expression. However, knockdown of either Fmrp or Dcp1a led to compromised differentiation. We also observed cross-regulation of decay versus storage mRNP granules; knockdown of Fmrp enhances accumulation of Dcp1a puncta, whereas knockdown of Dcp1a leads to increased Fmrp in puncta.Conclusions: Taken together, our results provide evidence that the balance of mRNA turnover versus utilization is specific for distinct cellular states.

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