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.

scholarly journals Chromatin accessibility dynamics and single cell RNA-Seq reveal new regulators of regeneration in neural progenitors

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Anneke Dixie Kakebeen ◽  
Alexander Daniel Chitsazan ◽  
Madison Corinne Williams ◽  
Lauren M Saunders ◽  
Andrea Elizabeth Wills
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Neural Progenitor Cells ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
Tail Regeneration ◽  
Cell Fate Decisions ◽  
Transcriptional Regulatory ◽  
Regulatory Dynamics

Vertebrate appendage regeneration requires precisely coordinated remodeling of the transcriptional landscape to enable the growth and differentiation of new tissue, a process executed over multiple days and across dozens of cell types. The heterogeneity of tissues and temporally-sensitive fate decisions involved has made it difficult to articulate the gene regulatory programs enabling regeneration of individual cell types. To better understand how a regenerative program is fulfilled by neural progenitor cells (NPCs) of the spinal cord, we analyzed pax6-expressing NPCs isolated from regenerating Xenopus tropicalis tails. By intersecting chromatin accessibility data with single-cell transcriptomics, we find that NPCs place an early priority on neuronal differentiation. Late in regeneration, the priority returns to proliferation. Our analyses identify Pbx3 and Meis1 as critical regulators of tail regeneration and axon organization. Overall, we use transcriptional regulatory dynamics to present a new model for cell fate decisions and their regulators in NPCs during regeneration.

scholarly journals Genomic insights into chromatin reprogramming to totipotency in embryos

2018 ◽  
Vol 218 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Sabrina Ladstätter ◽  
Kikuë Tachibana
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Epigenetic Reprogramming ◽  
Mammalian Embryo ◽  
Cell Fate Decisions ◽  
A Cell ◽  
Early Mouse ◽  
Chromatin Reprogramming

The early embryo is the natural prototype for the acquisition of totipotency, which is the potential of a cell to produce a whole organism. Generation of a totipotent embryo involves chromatin reorganization and epigenetic reprogramming that alter DNA and histone modifications. Understanding embryonic chromatin architecture and how this is related to the epigenome and transcriptome will provide invaluable insights into cell fate decisions. Recently emerging low-input genomic assays allow the exploration of regulatory networks in the sparsely available mammalian embryo. Thus, the field of developmental biology is transitioning from microscopy to genome-wide chromatin descriptions. Ultimately, the prototype becomes a unique model for studying fundamental principles of development, epigenetic reprogramming, and cellular plasticity. In this review, we discuss chromatin reprogramming in the early mouse embryo, focusing on DNA methylation, chromatin accessibility, and higher-order chromatin structure.

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 Identification of a Cell Death Pathway in Candida albicans during the Response to Pheromone

2010 ◽  
Vol 9 (11) ◽  
pp. 1690-1701 ◽  
Author(s):  
Kevin Alby ◽  
Dana Schaefer ◽  
Racquel Kim Sherwood ◽  
Stephen K. Jones ◽  
Richard J. Bennett
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Laboratory Strain ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Yeast Cells ◽  
Phenotypic Switching ◽  
Morphological Response ◽  
Content Type ◽  
Cell Death Pathway

ABSTRACT Mating in hemiascomycete yeasts involves the secretion of pheromones that induce sexual differentiation in cells of the opposite mating type. Studies in Saccharomyces cerevisiae have revealed that a subpopulation of cells experiences cell death during exposure to pheromone. In this work, we tested whether the phenomenon of pheromone-induced death (PID) also occurs in the opportunistic pathogen Candida albicans. Mating in C. albicans is uniquely regulated by white-opaque phenotypic switching; both cell types respond to pheromone, but only opaque cells undergo the morphological transition and cell conjugation. We show that approximately 20% of opaque cells, but not white cells, of laboratory strain SC5314 experience pheromone-induced death. Furthermore, analysis of mutant strains revealed that PID was significantly reduced in strains lacking Fig1 or Fus1 transmembrane proteins that are induced during the mating process and, we now show, are necessary for efficient mating in C. albicans. The level of PID was also Ca2+ dependent, as chelation of Ca2+ ions increased cell death to almost 50% of the population. However, in contrast to S. cerevisiae PID, pheromone-induced killing of C. albicans cells was largely independent of signaling via the Ca2+-dependent protein phosphatase calcineurin, even when combined with the loss of Cmk1 and Cmk2 proteins. Finally, we demonstrate that levels of PID vary widely between clinical isolates of C. albicans, with some strains experiencing close to 70% cell death. We discuss these findings in light of the role of prodeath and prosurvival pathways operating in yeast cells undergoing the morphological response to pheromone.

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.

scholarly journals Endogenous fluctuations of OCT4 and SOX2 bias pluripotent cell fate decisions

2018 ◽  
Author(s):  
Daniel Strebinger ◽  
Cédric Deluz ◽  
Elias T. Friman ◽  
Subashika Govindan ◽  
Andrea B. Alber ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Es Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Directed Differentiation ◽  
Es Cell ◽  
Endogenous Fluctuations ◽  
Cell Fate Decisions ◽  
Oct4 Protein

AbstractSOX2 and OCT4 are pioneer transcription factors playing a key role in embryonic stem (ES) cell self-renewal and differentiation. However, how temporal fluctuations in their expression levels bias lineage commitment is unknown. Here we generated knock-in reporter fusion ES cell lines allowing to monitor endogenous SOX2 and OCT4 protein fluctuations in living cells and to determine their impact on mesendodermal and neuroectodermal commitment. We found that small differences in SOX2 and OCT4 levels impact cell fate commitment in G1 but not in S phase. Elevated SOX2 levels modestly increased neuroectodermal commitment and decreased mesendodermal commitment upon directed differentiation. In contrast, elevated OCT4 levels strongly biased ES cell towards both neuroectodermal and mesendodermal fates. Using ATAC-seq on ES cells gated for different endogenous SOX2 and OCT4 levels, we found that high OCT4 levels increased chromatin accessibility at differentiation-associated enhancers. This suggests that small endogenous fluctuations of pioneer transcription factors can bias cell fate decisions by concentration-dependent priming of differentiation-associated enhancers.

scholarly journals Genetic control of pluripotency epigenome determines differentiation bias in mouse embryonic stem cells

2021 ◽  
Author(s):  
Candice Byers ◽  
Catrina Spruce ◽  
Haley J. Fortin ◽  
Anne Czechanski ◽  
Steven C. Munger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Genetic Regulation ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Embryoid Bodies ◽  
Cell Fate Decisions

AbstractGenetically diverse pluripotent stem cells (PSCs) display varied, heritable responses to differentiation cues in the culture environment. By harnessing these disparities through derivation of embryonic stem cells (ESCs) from the BXD mouse genetic reference panel, along with C57BL/6J (B6) and DBA/2J (D2) parental strains, we demonstrate genetically determined biases in lineage commitment and identify major regulators of the pluripotency epigenome. Upon transition to formative pluripotency using epiblast-like cells (EpiLCs), B6 quickly dissolves naïve networks adopting gene expression modules indicative of neuroectoderm lineages; whereas D2 retains aspects of naïve pluripotency with little bias in differentiation. Genetic mapping identifies 6 major trans-acting loci co-regulating chromatin accessibility and gene expression in ESCs and EpiLCs, indicating a common regulatory system impacting cell state transition. These loci distally modulate occupancy of pluripotency factors, including TRIM28, P300, and POU5F1, at hundreds of regulatory elements. One trans-acting locus on Chr 12 primarily impacts chromatin accessibility in ESCs; while in EpiLCs the same locus subsequently influences gene expression, suggesting early chromatin priming. Consequently, the distal gene targets of this locus are enriched for neurogenesis genes and were more highly expressed when cells carried B6 haplotypes at this Chr 12 locus, supporting genetic regulation of biases in cell fate. Spontaneous formation of embryoid bodies validated this with B6 showing a propensity towards neuroectoderm differentiation and D2 towards definitive endoderm, confirming the fundamental importance of genetic variation influencing cell fate decisions.

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