scholarly journals Drosophila anion exchanger 2 is required for proper ovary development and oogenesis

2018 ◽  
Author(s):  
Marimar Benitez ◽  
Sumitra Tatapudy ◽  
Diane L. Barber ◽  
Todd Nystul
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Anion Exchanger ◽  
Cell Biology ◽  
Null Alleles ◽  
Ovary Development ◽  
Cell Fate Decisions ◽  
Daughter Cells ◽  
Differentiated Cells ◽  
Anion Exchanger 2

AbstractUnderstanding how cell fate decisions are regulated is a central question in stem cell biology. Recent studies have demonstrated that intracellular pH (pHi) dynamics contribute to this process. Indeed, the pHi of cells within a tissue is not simply a consequence of chemical reactions in the cytoplasm and other cellular activity, but is actively maintained at a specific setpoint in each cell type. We found previously that the pHi of cells in the follicle stem cell (FSC) lineage in the Drosophila ovary increases progressively during differentiation from an average of 6.8 in the FSCs, to 7.0 in newly produced daughter cells, to 7.3 in more differentiated cells. Two major regulators of pHi in this lineage are Drosophila sodium-proton exchanger 2 (dNhe2) and a previously uncharacterized gene, CG8177, that is homologous to mammalian anion exchanger 2 (AE2). Based on this homology, we named the gene ae2. Here, we generated null alleles of ae2 and found that homozygous mutant flies are viable but have severe defects in ovary development and adult oogenesis. Specifically, we find that ae2 null flies have smaller ovaries, reduced fertility, and impaired follicle formation. In addition, we find that the follicle formation defect can be suppressed by a decrease in dNhe2 copy number and enhanced by the overexpression of dNhe2, suggesting that this phenotype is due to the dysregulation of pHi. These findings support the emerging idea that pHi dynamics regulate cell fate decisions and our studies provide new genetic tools to investigate the mechanisms by which this occurs.

scholarly journals Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch regulatory loop

2018 ◽  
Vol 217 (9) ◽  
pp. 3285-3300 ◽  
Author(s):  
Sebastian Wissel ◽  
Heike Harzer ◽  
François Bonnay ◽  
Thomas R. Burkard ◽  
Ralph A. Neumüller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Cell Biology ◽  
Transcriptional Profiling ◽  
Nervous System Development ◽  
Time Resolved ◽  
Daughter Cells ◽  
Regulatory Loop

Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates. By screening for coregulated protein complexes, we identify vacuolar-type H+–ATPase (v-ATPase) among the first and most significantly down-regulated complexes in differentiating daughter cells. We show that v-ATPase is essential for NB growth and persistent activity of the Notch signaling pathway. Our data suggest that v-ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut. We provide a unique resource for investigating neural stem cell biology and demonstrate that cell fate changes can be induced by transcriptional regulation of basic, cell-essential pathways.

scholarly journals Cytokinetic Abscission Regulation in Neural Stem Cells and Tissue Development

2021 ◽  
Author(s):  
Katrina C. McNeely ◽  
Noelle D. Dwyer
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Cell Polarity ◽  
Cell Biology ◽  
Tissue Growth ◽  
Developmentally Regulated ◽  
Daughter Cells ◽  
Fate Determinants

Abstract Purpose of Review How stem cells balance proliferation with differentiation, giving rise to specific daughter cells during development to build an embryo or tissue, remains an open question. Here, we discuss recent evidence that cytokinetic abscission regulation in stem cells, particularly neural stem cells (NSCs), is part of the answer. Abscission is a multi-step process mediated by the midbody, a microtubule-based structure formed in the intercellular bridge between daughter cells after mitosis. Recent Findings Human mutations and mouse knockouts in abscission genes reveal that subtle disruptions of NSC abscission can cause brain malformations. Experiments in several epithelial systems have shown that midbodies serve as scaffolds for apical junction proteins and are positioned near apical membrane fate determinants. Abscission timing is tightly controlled and developmentally regulated in stem cells, with delayed abscission in early embryos and faster abscission later. Midbody remnants (MBRs) contain over 400 proteins and may influence polarity, fate, and ciliogenesis. Summary As NSCs and other stem cells build tissues, they tightly regulate three aspects of abscission: midbody positioning, duration, and MBR handling. Midbody positioning and remnants establish or maintain cell polarity. MBRs are deposited on the apical membranes of epithelia, can be released or internalized by surrounding cells, and may sequester fate determinants or transfer information between cells. Work in cell lines and simpler systems has shown multiple roles for abscission regulation influencing stem cell polarity, potency, and daughter fates during development. Elucidating how the abscission process influences cell fate and tissue growth is important for our continued understanding of brain development and stem cell biology.

scholarly journals Cell reprogramming modelled as transitions in a hierarchy of cell cycles

2016 ◽  
Author(s):  
R. Hannam ◽  
A. Annibale ◽  
R. Kühn
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
A Priori ◽  
Cell Types ◽  
Cell Reprogramming ◽  
Cell Cycles ◽  
Cell Fate Decisions ◽  
Differentiated Cells ◽  
Cellular Environment ◽  
Experimental Findings

We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. This work aims to bridge this gap by modelling cell types as a set of hierarchically related dynamical attractors representing cell cycles. Stages of the cell cycle are characterised by the configuration of gene expression levels, and reprogramming corresponds to triggering transitions between such configurations. Two mechanisms were found for reprogramming in a two level hierarchy: cycle specific perturbations and a noise induced switching. The former corresponds to a directed perturbation that induces a transition into a cycle-state of a different cell type in the potency hierarchy (mainly a stem cell) whilst the latter is a priori undirected and could be induced, e.g., by a (stochastic) change in the cellular environment. These reprogramming protocols were found to be effective in large regimes of the parameter space and make specific predictions concerning reprogramming dynamics which are broadly in line with experimental findings.

scholarly journals Conditionally immortalised leukaemia initiating cells co-expressing Hoxa9/Meis1 demonstrate microenvironmental adaptation properties ex vivo while maintaining myelomonocytic memory

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maike Stahlhut ◽  
Teng Cheong Ha ◽  
Ekaterina Takmakova ◽  
Michael A. Morgan ◽  
Adrian Schwarzer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Cell Lines ◽  
Cell Biology ◽  
Ex Vivo ◽  
Haematopoietic Stem Cell ◽  
Transcriptional Dysregulation ◽  
Conditional Gene Expression ◽  
Exponential Expansion ◽  
Drug Dependent

AbstractRegulation of haematopoietic stem cell fate through conditional gene expression could improve understanding of healthy haematopoietic and leukaemia initiating cell (LIC) biology. We established conditionally immortalised myeloid progenitor cell lines co-expressing constitutive Hoxa9.EGFP and inducible Meis1.dTomato (H9M-ciMP) to study growth behaviour, immunophenotype and morphology under different cytokine/microenvironmental conditions ex vivo upon doxycycline (DOX) induction or removal. The vector design and drug-dependent selection approach identified new retroviral insertion (RVI) sites that potentially collaborate with Meis1/Hoxa9 and define H9M-ciMP fate. For most cell lines, myelomonocytic conditions supported reversible H9M-ciMP differentiation into neutrophils and macrophages with DOX-dependent modulation of Hoxa9/Meis1 and CD11b/Gr-1 expression. Here, up-regulation of Meis1/Hoxa9 promoted reconstitution of exponential expansion of immature H9M-ciMPs after DOX reapplication. Stem cell maintaining conditions supported selective H9M-ciMP exponential growth. H9M-ciMPs that had Ninj2 RVI and were cultured under myelomonocytic or stem cell maintaining conditions revealed the development of DOX-dependent acute myeloid leukaemia in a murine transplantation model. Transcriptional dysregulation of Ninj2 and distal genes surrounding RVI (Rad52, Kdm5a) was detected. All studied H9M-ciMPs demonstrated adaptation to T-lymphoid microenvironmental conditions while maintaining immature myelomonocytic features. Thus, the established system is relevant to leukaemia and stem cell biology.

scholarly journals Context-dependent roles of YAP/TAZ in stem cell fates and cancer

2021 ◽  
Author(s):  
Lucy LeBlanc ◽  
Nereida Ramirez ◽  
Jonghwan Kim
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Control Cell ◽  
Substantial Portion ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Cell Death Pathways ◽  
Multiple Context ◽  
Cancer Cell Survival ◽  
Context Dependent

AbstractHippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

scholarly journals The Winding Road of Cardiac Regeneration—Stem Cell Omics in the Spotlight

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 255 ◽  
Author(s):  
Miruna Mihaela Micheu ◽  
Alina Ioana Scarlatescu ◽  
Alexandru Scafa-Udriste ◽  
Maria Dorobantu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Great Promise ◽  
Omics Data

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.

scholarly journals Characterization of histone inheritance patterns in the Drosophila female germline

2020 ◽  
Author(s):  
Elizabeth W. Kahney ◽  
Lydia Sohn ◽  
Kayla Viets-Layng ◽  
Robert Johnston ◽  
Xin Chen
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Single Gene ◽  
Asymmetric Division ◽  
Germline Stem Cell ◽  
Inheritance Patterns ◽  
Daughter Cells ◽  
Dividing Cells ◽  
Female Germline

ABSTRACTStem cells have the unique ability to undergo asymmetric division which produces two daughter cells that are genetically identical, but commit to different cell fates. The loss of this balanced asymmetric outcome can lead to many diseases, including cancer and tissue dystrophy. Understanding this tightly regulated process is crucial in developing methods to treat these abnormalities. Here, we report that produced from a Drosophila female germline stem cell asymmetric division, the two daughter cells differentially inherit histones at key genes related to either maintaining the stem cell state or promoting differentiation, but not at constitutively active or silenced genes. We combined histone labeling with DNA Oligopaints to distinguish old versus new histone distribution and visualize their inheritance patterns at single-gene resolution in asymmetrically dividing cells in vivo. This strategy can be widely applied to other biological contexts involving cell fate establishment during development or tissue homeostasis in multicellular organisms.

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