scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

AbstractTissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

scholarly journals Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cell Therapy ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Stem Cell Maintenance ◽  
Selection Of

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

scholarly journals Loss of Mob1a/b impairs the differentiation of mouse embryonic stem cells into the three germ layer lineages

2019 ◽  
Vol 51 (11) ◽  
pp. 1-12 ◽  
Author(s):  
June Sung Bae ◽  
Sun Mi Kim ◽  
Yoon Jeon ◽  
Juyeon Sim ◽  
Ji Yun Jang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hippo Pathway ◽  
Critical Role ◽  
Embryonic Stem ◽  
Mouse Escs ◽  
Germ Layers ◽  
Stem Cell Maintenance ◽  
The Hippo Pathway ◽  
Cell Maintenance

AbstractThe Hippo pathway plays a crucial role in cell proliferation and apoptosis and can regulate stem cell maintenance and embryonic development. MOB kinase activators 1A and 1B (Mob1a/b) are key components of the Hippo pathway, whose homozygous deletion in mice causes early embryonic lethality at the preimplantation stage. To investigate the role of Mob1a/b in stem cell maintenance and differentiation, an embryonic stem cell (ESC) clone in which Mob1a/b could be conditionally depleted was generated and characterized. Although Mob1a/b depletion did not affect the stemness or proliferation of mouse ESCs, this depletion caused defects in differentiation into the three germ layers. Yap knockdown rescued the in vitro and in vivo defects in differentiation caused by Mob1a/b depletion, suggesting that differentiation defects caused by Mob1a/b depletion were Yap-dependent. In teratoma experiments, Yap knockdown in Mob1a/b-depleted ESCs partially restored defects in differentiation, indicating that hyperactivation of Taz, another effector of the Hippo pathway, inhibited differentiation into the three germ layers. Taken together, these results suggest that Mob1a/b or Hippo signaling plays a critical role in the differentiation of mouse ESCs into the three germ layers, which is dependent on Yap. These close relationship of the Hippo pathway with the differentiation of stem cells supports its potential as a therapeutic target in regenerative medicine.

scholarly journals Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions in Drosophila male germline stem cells

2012 ◽  
Vol 23 (8) ◽  
pp. 1524-1532 ◽  
Author(s):  
Therese M. Roth ◽  
C.-Y. Ason Chiang ◽  
Mayu Inaba ◽  
Hebao Yuan ◽  
Viktoria Salzmann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Germline Stem Cells ◽  
Self Renewal ◽  
Stem Cell Regulation ◽  
Male Germline ◽  
Male Germline Stem Cells ◽  
Nutrient Conditions

Drosophila male germline stem cells (GSCs) divide asymmetrically, balancing self-renewal and differentiation. Although asymmetric stem cell division balances between self-renewal and differentiation, it does not dictate how frequently differentiating cells must be produced. In male GSCs, asymmetric GSC division is achieved by stereotyped positioning of the centrosome with respect to the stem cell niche. Recently we showed that the centrosome orientation checkpoint monitors the correct centrosome orientation to ensure an asymmetric outcome of the GSC division. When GSC centrosomes are not correctly oriented with respect to the niche, GSC cell cycle is arrested/delayed until the correct centrosome orientation is reacquired. Here we show that induction of centrosome misorientation upon culture in poor nutrient conditions mediates slowing of GSC cell proliferation via activation of the centrosome orientation checkpoint. Consistently, inactivation of the centrosome orientation checkpoint leads to lack of cell cycle slowdown even under poor nutrient conditions. We propose that centrosome misorientation serves as a mediator that transduces nutrient information into stem cell proliferation, providing a previously unappreciated mechanism of stem cell regulation in response to nutrient conditions.

Maintenance of Pluripotent Stem Cells is Influenced by Ser/Thr Metabolism

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-43-SCI-43
Author(s):  
Lewis C. Cantley
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Isocitrate Dehydrogenase 1 ◽  
Advisory Committees ◽  
Metabolic Intermediates ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Methylation Of Dna

Abstract Recent studies have suggested not only that stem cells have different metabolic requirements than terminally differentiated cells, but also that metabolic intermediates may play a role in the maintenance of stem cells. It has long been clear that changes in acetylation and methylation of histones, as well as methylation of DNA play critical roles in deciding cell fate. The availability of critical intermediates in metabolism, especially S-adenosylmethionine (SAM), acetyl-CoA, nicotinamide adenine dinucleotide (NAD) and a-ketoglutarate play critical roles in modulating acetylation and methylation of histones and methylation of DNA. In the course of evaluating an unusual requirement of threonine (Thr) for the growth of murine embryonic stem cells, we found that metabolism of Thr to glycine (Gly) and the subsequent use of the methyl group of Gly for converting homocysteine to methionine is critical for maintaining high levels of SAM and low levels of S-adenosyl-homocysteine. Importantly, depletion of Thr from the media resulted in decreased tri-methylation of histone H3 lysine-4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate. Demethylation of histones and DNA can also be controlled by metabolic intermediates. Mutated forms of isocitrate dehydrogenase 1 (IDH1) and IDH2 that drive acute myeloid leukemia (AML) and other cancers, produce an oncometabolite (2-hydrogyglutarate) that can compete with the a-ketoglutarate requirement for enzymes involved in hydroxy-methylation and subsequent demethylation of DNA and histones. Recent studies indicate that 2-hydroxyglutarate plays a role in blocking differentiation of cancer cells. These and other observations linking intermediates in metabolism to stem cell maintenance will be discussed. Disclosures Cantley: Agios Pharmaceuticals: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Somatic signaling mediated by fs(1)Yb is essential for germline stem cell maintenance during Drosophila oogenesis

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1833-1844 ◽  
Author(s):  
F.J. King ◽  
H. Lin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Genomic Region ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Drosophila Oogenesis ◽  
Stem Cell Maintenance ◽  
Terminal Filament ◽  
Potential Signal ◽  
Cell Maintenance

Drosophila oogenesis starts when a germline stem cell divides asymmetrically to generate a daughter germline stem cell and a cystoblast that will develop into a mature egg. We show that the fs(1)Yb gene is essential for the maintenance of germline stem cells during oogenesis. We delineate fs(1)Yb within a 6.4 kb genomic region by transgenic rescue experiments. fs(1)Yb encodes a 4.1 kb RNA that is present in the third instar larval, pupal and adult stages, consistent with its role in regulating germline stem cells during oogenesis. Germline clonal analysis shows that all fs(1)Yb mutations are soma-dependent. In the adult ovary, fs(1)Yb is specifically expressed in the terminal filament cells, suggesting that fs(1)Yb acts in these signaling cells to maintain germline stem cells. fs(1)Yb encodes a novel hydrophilic protein with no potential signal peptide or transmembrane domains, suggesting that this protein is not itself a signal but a key component of the signaling machinery for germline stem cell maintenance.

Maintenance of pluripotential embryonic stem cells by stem cell selection

1998 ◽  
Vol 10 (8) ◽  
pp. 527 ◽  
Author(s):  
Peter Mountford ◽  
Jennifer Nichols ◽  
Branko Zevnik ◽  
Carmel O'Brien ◽  
Austin Smith
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Es Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Stem Cell Population ◽  
Cell Selection ◽  
Es Cell ◽  
Mammalian Embryo ◽  
Differentiated Cells

As gastrulation proceeds, pluripotential stem cells with the capacity to contribute to all primary germ layers disappear from the mammalian embryo. The extinction of pluripotency also occurs during the formation of embryoid bodies from embryonic stem (ES) cells. In this report we show that if the initial differentiated progeny are removed from ES cell aggregates, further differentiation does not proceed and the stem cell population persists and expands. Significantly, the presence of even minor populations of differentiated cells lead to the complete loss of stem cells from the cultures. This finding implies that the normal elimination of pluripotent cells is dictated by inductive signals provided by differentiated progeny. We have exploited this observation to develop a strategy for the isolation of pluripotential cells. This approach, termed stem cell selection, may have widespread applicability to the derivation and propagation of stem cells.

scholarly journals The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress

2021 ◽  
Author(s):  
Ernesto Llamas ◽  
Salvador Torres-Montilla ◽  
Hyun Ju Lee ◽  
María Victoria Barja ◽  
Elena Schlimgen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Protein Aggregation ◽  
Cell Function ◽  
Proteasome Inhibition ◽  
Stem Cell Maintenance ◽  
Proteotoxic Stress ◽  
Differentiated Cells ◽  
Plant Stem ◽  
Chaperone Network

AbstractThe biological purpose of plant stem cells is to maintain themselves while providing new pools of differentiated cells that form organs and rejuvenate or replace damaged tissues1-3. Protein homeostasis, or proteostasis, is required for cell function and viability4-7. However, the link between proteostasis and plant stem cell identity remains unknown. In contrast to their differentiated counterparts, we find that root stem cells can prevent the accumulation of aggregated proteins even under proteotoxic stress conditions such as heat stress or proteasome inhibition. Notably, root stem cells exhibit enhanced expression of distinct chaperones that maintain proteome integrity. Particularly, intrinsic high levels of the TRiC/CCT chaperonin determine stem cell maintenance and their remarkable ability to suppress protein aggregation. Overexpression of CCT8, a key activator of TRiC/CCT assembly8, is sufficient to ameliorate protein aggregation in differentiated cells and confer resistance to proteotoxic stress in plants. Taken together, our results indicate that enhanced proteostasis mechanisms in stem cells could be an important requirement for plants to persist under extreme environmental conditions and reach extreme long ages. Thus, proteostasis of stem cells could provide insights to design and breed plants tolerant to environmental challenges caused by the climate change.

scholarly journals Heparan sulfate regulates the number and centrosome positioning of Drosophila male germline stem cells

2016 ◽  
Vol 27 (6) ◽  
pp. 888-896 ◽  
Author(s):  
Daniel C. Levings ◽  
Takeshi Arashiro ◽  
Hiroshi Nakato
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heparan Sulfate ◽  
Molecular Mechanisms ◽  
Asymmetric Division ◽  
Germline Stem Cells ◽  
Cell Behaviors ◽  
Male Germline ◽  
Drosophila Testis ◽  
Stem Cell Division

Stem cell division is tightly controlled via secreted signaling factors and cell adhesion molecules provided from local niche structures. Molecular mechanisms by which each niche component regulates stem cell behaviors remain to be elucidated. Here we show that heparan sulfate (HS), a class of glycosaminoglycan chains, regulates the number and asymmetric division of germline stem cells (GSCs) in the Drosophila testis. We found that GSC number is sensitive to the levels of 6- O sulfate groups on HS. Loss of 6- O sulfation also disrupted normal positioning of centrosomes, a process required for asymmetric division of GSCs. Blocking HS sulfation specifically in the niche, termed the hub, led to increased GSC numbers and mispositioning of centrosomes. The same treatment also perturbed the enrichment of Apc2, a component of the centrosome-anchoring machinery, at the hub–GSC interface. This perturbation of the centrosome-anchoring process ultimately led to an increase in the rate of spindle misorientation and symmetric GSC division. This study shows that specific HS modifications provide a novel regulatory mechanism for stem cell asymmetric division. The results also suggest that HS-mediated niche signaling acts upstream of GSC division orientation control.

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