scholarly journals Asymmetric Distribution of Glucose Transporter mRNA Provides Growth Advantage

2018 ◽  
Author(s):  
Timo Stahl ◽  
Stefan Hümmer ◽  
Nikolaus Ehrenfeuchter ◽  
Geoffrey Fucile ◽  
Anne Spang
Keyword(s):  
Cell Fate ◽  
Glucose Transporter ◽  
Cell Types ◽  
Mrna Localization ◽  
The Other ◽  
Asymmetric Distribution ◽  
Hexose Transporter ◽  
Cell Fate Decisions ◽  
Glucose Transporter Mrna ◽  
Pka Pathway

AbstractAsymmetric localization of mRNA is important for cell fate decisions in eukaryotes and provides the means for localized protein synthesis in a variety of cell types. Here we show that hexose transporter mRNAs are retained in the mother cell of S. cerevisiae until metaphase-anaphase transition (MAT) and then are released into the bud. The retained mRNA was translationally inactive but bound to ribosomes before MAT. Importantly, when cells were shifted from starvation to glucose-rich conditions, HXT2 mRNA, but none of the other HXT mRNAs, was enriched in the bud after MAT. This enrichment was dependent on the Ras/cAMP/PKA pathway, the APC ortholog Kar9 and nuclear segregation into the bud. Competition experiments between strains that only expressed one hexose transporter at a time revealed that HXT2 only cells grow faster than their counterparts when released from starvation. Therefore, asymmetric distribution of HXT2 mRNA provides a growth advantage for young daughters, who are better prepared for nutritional changes in the environment. Our data provide evidence that asymmetric mRNA localization is an important factor in determining cellular fitness.

scholarly journals The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday
Keyword(s):  
Candida Albicans ◽  
Cell Fate ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Chromatin Remodelers ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Simple Model System

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3865-3876
Author(s):  
M.S. Rones ◽  
K.A. McLaughlin ◽  
M. Raffin ◽  
M. Mercola
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Cell Fate ◽  
Notch Pathway ◽  
Cell Types ◽  
Myocardial Cell ◽  
Dominant Negative ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Heart Field

Notch signaling mediates numerous developmental cell fate decisions in organisms ranging from flies to humans, resulting in the generation of multiple cell types from equipotential precursors. In this paper, we present evidence that activation of Notch by its ligand Serrate apportions myogenic and non-myogenic cell fates within the early Xenopus heart field. The crescent-shaped field of heart mesoderm is specified initially as cardiomyogenic. While the ventral region of the field forms the myocardial tube, the dorsolateral portions lose myogenic potency and form the dorsal mesocardium and pericardial roof (Raffin, M., Leong, L. M., Rones, M. S., Sparrow, D., Mohun, T. and Mercola, M. (2000) Dev. Biol., 218, 326–340). The local interactions that establish or maintain the distinct myocardial and non-myocardial domains have never been described. Here we show that Xenopus Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early heart field. Conditional activation or inhibition of the Notch pathway with inducible dominant negative or active forms of the RBP-J/Suppressor of Hairless [Su(H)] transcription factor indicated that activation of Notch feeds back on Serrate1 gene expression to localize transcripts more dorsolaterally than those of Notch1, with overlap in the region of the developing mesocardium. Moreover, Notch pathway activation decreased myocardial gene expression and increased expression of a marker of the mesocardium and pericardial roof, whereas inhibition of Notch signaling had the opposite effect. Activation or inhibition of Notch also regulated contribution of individual cells to the myocardium. Importantly, expression of Nkx2. 5 and Gata4 remained largely unaffected, indicating that Notch signaling functions downstream of heart field specification. We conclude that Notch signaling through Su(H) suppresses cardiomyogenesis and that this activity is essential for the correct specification of myocardial and non-myocardial cell fates.

scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

scholarly journals Hypoxia-Inducible Factors 1α and 2α Regulate Trophoblast Differentiation

2005 ◽  
Vol 25 (23) ◽  
pp. 10479-10491 ◽  
Author(s):  
Karen D. Cowden Dahl ◽  
Benjamin H. Fryer ◽  
Fiona A. Mack ◽  
Veerle Compernolle ◽  
Emin Maltepe ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Placental Development ◽  
Cell Fates ◽  
Trophoblast Stem Cells ◽  
Cell Fate Decisions ◽  
Hypoxic Environment ◽  
Life Threatening

ABSTRACT Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF1α and HIF2α, are essential for determining murine placental cell fates. HIF is a heterodimer composed of HIFα and HIFβ (ARNT) subunits. Placentas from Arnt − / − and Hif1α − / − Hif2α −/− embryos exhibit defective placental vascularization and aberrant cell fate adoption. HIF regulation of Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast giant cell differentiation. In the absence of Arnt or Hifα, trophoblast stem cells fail to generate these cell types and become labyrinthine trophoblasts instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, and cell fate decisions, demonstrating that O2 tension is a critical regulator of trophoblast lineage determination. This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia.

scholarly journals Niche mediated integrin signaling supports steady state hematopoiesis in spleen

2020 ◽  
Author(s):  
Shubham Haribhau Mehatre ◽  
Irene Mariam Roy ◽  
Atreyi Biswas ◽  
Devila Prit ◽  
Sarah Schouteden ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Integrin Signaling ◽  
White Pulp ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Functional Regulation

AbstractOutside-in integrin signaling regulates cell fate decisions in a variety of cell types, including hematopoietic stem cells (HSCs). Our earlier published studies showed that interruption of Periostin (POSTN) and Integrin-αv (ITGAV) interaction induces faster proliferation in HSCs with developmental stage dependent functional effects. Here, we examined the role of POSTN-ITGAV axis in lympho-hematopoietic activity in spleen that hosts rare population of HSCs, the functional regulation of which is not clearly known. Vav-iCre mediated deletion of Itgav in hematopoietic system led to higher proliferation rates, resulting in increased frequency of primitive HSCs in adult spleen. However, in vitro CFU-C assays demonstrated a poorer differentiation potential following Itgav deletion. This also led to a decrease in the white pulp area with a significant decline in the B-cell numbers. Systemic deletion of its ligand, POSTN, phenocopied the effects noted in Vav-Itgav−/− mice. Histological examination of Postn deficient spleen also showed increase in the spleen trabecular areas. Surprisingly, these were the myofibroblasts of the trabecular and capsular areas that expressed high levels of POSTN within the spleen tissue. In addition, vascular smooth muscle cells also expressed POSTN. Through CFU-S12 assays, we showed that hematopoietic support potential of stroma in Postn deficient splenic hematopoietic niche was defective. Overall, we demonstrate that POSTN-ITGAV interaction plays important role in spleen lympho-hematopoiesis.

scholarly journals Epigenetic Control of Mesenchymal Stromal Cell Fate Decision

2021 ◽  
Author(s):  
Haoli Ying ◽  
Ruolang Pan ◽  
Ye Chen
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Connective Tissues ◽  
Differentiation Potential ◽  
Cell Fate Decisions ◽  
Fate Decision ◽  
Msc Differentiation

Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering owing to their differentiation potential in various cell types. The therapeutic utility of MSCs hinges upon our understanding of the molecular mechanisms involved in cellular fate decisions. Thus, the elucidation of the regulation of MSC differentiation has attracted increasing attention in recent years. A variety of external cues contribute to the process of MSC differentiation, including chemical, physical, and biological factors. Among the multiple factors that are known to affect cell fate decisions, the epigenetic regulation of MSC differentiation has become a research hotspot. In this chapter, we summarize recent progress in the determination of the effects of epigenetic modification on the multilineage differentiation of MSCs.

Position dependent control of cell fate in the Fucus embryo: role of intercellular communication

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 1999-2008 ◽  
Author(s):  
F.Y. Bouget ◽  
F. Berger ◽  
C. Brownlee
Keyword(s):  
Cell Wall ◽  
Pattern Formation ◽  
Cell Fate ◽  
Intercellular Communication ◽  
Cell Types ◽  
Early Embryo ◽  
Cell Contact ◽  
Dependent Manner ◽  
Intact Cells ◽  
Cell Fate Decisions

The early embryo of the brown alga Fucus comprises two cell types, i. e. rhizoid and thallus which are morphogically and cytologically distinguishable. Previous work has pointed to the cell wall as a source of position-dependent information required for polarisation and fate determination in the zygote and 2-celled embryo. In this study we have analysed the mechanism(s) of cell fate control and pattern formation at later embryonic stages using a combination of laser microsurgery and microinjection. The results indicate that the cell wall is required for maintenance of pre-existing polarity in isolated intact cells. However, all cell types ultimately have the capacity to re-differentiate or regenerate rhizoid cells in response to ablation of neighbouring cells. This regeneration is regulated in a position-dependent manner and is strongly influenced by intercellular communication, probably involving transport or diffusion of inhibitory signals which appear to be essential for regulation of cell fate decisions. This type of cell-to-cell communication does not involve symplastic transport or direct cell-cell contact inhibition. Apoplastic diffusible gradients appear to be involved in pattern formation in the multicellular embryo.

Abstract 290: Microrna-199a and Glut1 are Differentially Expressed in Primary Human Arterial and Venous Endothelium and are Deregulated in Culture

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Matthew R Richardson ◽  
Xianyin Lai ◽  
Mervin C Yoder
Keyword(s):  
Cell Fate ◽  
Umbilical Cord ◽  
Glucose Transporter ◽  
Cell Types ◽  
Enzymatic Digestion ◽  
Protein Quantification ◽  
Human Umbilical Cord ◽  
Mrna Levels ◽  
Downstream Target ◽  
Glut1 Mrna

Introduction Studies over the last decade have established that the identity of arterial and venous endothelial cells (ECs) is governed by both genetic and environmental factors. Although the ephrin/Eph system is known to be a key determinant of that identity, it is unlikely that system is solely responsible for all the differences between arterial and venous ECs. Furthermore, microRNAs are becoming increasingly recognized for their important role in regulating gene expression and cell fate. We investigate here novel potential markers and regulators of arterial EC identity and the effects of environmental cues on these molecules. Methods ECs were freed from the basement membrane of human umbilical arteries and veins (HUAECs, HUVECs) (n=6) by enzymatic digestion and purified by flow cytometry (CD31+, CD45-) prior to lysis and quantitative PCR or analysis using HPLC-MS/MS. Protein quantification was performed using a proprietary software package (IdentiQuantXL TM ). HUVECs and HUAECs were harvested directly from umbilical cords and placed directly into collagen coated 6-well plates and cultured in standard conditions in EGM2. Results We found that microRNA-199a levels were 23 fold higher in HUVECs than HUAECs (p=0.0001). One of microRNA-199a’s theoretical downstream targets is GLUT1, a facilitative glucose transporter thought to be responsible for basal glucose uptake. GLUT1 mRNA and protein levels were significantly higher (5.5 and 4.3 fold, respectively) in HUAEC than HUVECs (p=0.00002). Using tissue immunohistochemistry (IHC) of we confirmed that GLUT1 expression is restricted to arterial ECs in human umbilical cord and adult peripheral artery and vein sections. Finally, GLUT1 mRNA levels are 2 fold higher in HUAECs than HUVECs in culture at P2 and levels decrease until P5 when they become equal indicating that culture has a homogenizing effect on endothelial heterogeneity. Conclusions MicroRNA-199a levels are higher in HUVECs than HUAECs and GLUT1, its downstream target, is higher in HUAECs both at the mRNA and protein level. Protein expression is restricted to arteries in both the new born umbilical cord and adult peripheral vessels. Importantly, expression in both cell types is downregulated and equilibrated by cell culture.

Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development

Development ◽  
1992 ◽  
Vol 115 (3) ◽  
pp. 737-744 ◽  
Author(s):  
F.F. Del Amo ◽  
D.E. Smith ◽  
P.J. Swiatek ◽  
M. Gendron-Maguire ◽  
R.J. Greenspan ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mouse Embryo ◽  
Transmembrane Protein ◽  
Neuronal Cell ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Mouse Development ◽  
Cell Fate Decisions ◽  
Early Mouse ◽  
Partial Cdna Clone

The Notch gene of Drosophila encodes a large transmembrane protein involved in cell-cell interactions and cell fate decisions in the Drosophila embryo. To determine if a gene homologous to Drosophila Notch plays a role in early mouse development, we screened a mouse embryo cDNA library with probes from the Xenopus Notch homolog, Xotch. A partial cDNA clone encoding the mouse Notch homolog, which we have termed Motch, was used to analyze expression of the Motch gene. Motch transcripts were detected in a wide variety of adult tissues, which included derivatives of all three germ layers. Differentiation of P19 embryonal carcinoma cells into neuronal cell types resulted in increased expression of Motch RNA. In the postimplantation mouse embryo Motch transcripts were first detected in mesoderm at 7.5 days post coitum (dpc). By 8.5 dpc, transcript levels were highest in presomitic mesoderm, mesenchyme and endothelial cells, while much lower levels were detected in neuroepithelium. In contrast, at 9.5 dpc, neuroepithelium was a major site of Motch expression. Transcripts were also abundant in cell types derived from neural crest. These data suggest that the Motch gene plays multiple roles in patterning and differentiation of the early postimplantation mouse embryo.

scholarly journals Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene

2010 ◽  
Vol 298 (6) ◽  
pp. C1560-C1571 ◽  
Author(s):  
Mounir Chehtane ◽  
Annette R. Khaled
Keyword(s):  
Cell Fate ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Control Cell ◽  
Rapid Decline ◽  
Hexokinase Ii ◽  
Cell Fate Decisions ◽  
Glut 1 ◽  
Interleukin 7 ◽  
Atp Levels

The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic activity in support of its vital function in lymphocytes. We observed that IL-7 deprivation caused a rapid decline in the metabolism of glucose that was attributable to loss of intracellular glucose retention. To identify the transducer of the IL-7 metabolic signal, we examined the expression of three important regulators of glucose metabolism, the glucose transporter GLUT-1 and two glycolytic enzymes, hexokinase II (HXKII) and phosphofructokinase-1 (PFK-1), using an IL-7-dependent T-cell line and primary lymphocytes. We found that in lymphocytes deprived of IL-7 loss of glucose uptake correlated with decreased expression of HXKII. Readdition of IL-7 to cytokine-deprived lymphocytes restored the transcription of the HXKII gene within 2 h, but not that of GLUT-1 or PFK-1. IL-7-mediated increases in HXKII, but not GLUT-1 or PFK-1, were also observed at the protein level. Inhibition of HXKII with 3-bromopyruvate or specific small-interfering RNA decreased glucose utilization, as well as ATP levels, in the presence of IL-7, whereas overexpression of HXKII, but not GLUT-1, restored glucose retention and increased ATP levels in the absence of IL-7. We conclude that IL-7 controls glucose utilization by regulating the gene expression of HXKII, suggesting a mechanism by which IL-7 supports bioenergetics that control cell fate decisions in lymphocytes.

Sign in / Sign up

Export Citation Format

Share Document