scholarly journals Transcriptome Remodeling of Differentiated Cells during Chronological Ageing of Yeast Colonies: New Insights into Metabolic Differentiation

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Derek Wilkinson ◽  
Jana Maršíková ◽  
Otakar Hlaváček ◽  
Gregor D. Gilfillan ◽  
Eva Ježková ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Rna Seq ◽  
Differentiated Cells ◽  
L Cell ◽  
Homogeneous Cell ◽  
Cell Subpopulations ◽  
Cell Colony ◽  
Homogeneous Cell Population

We present the spatiotemporal metabolic differentiation of yeast cell subpopulations from upper, lower, and margin regions of colonies of different ages, based on comprehensive transcriptomic analysis. Furthermore, the analysis was extended to include smaller cell subpopulations identified previously by microscopy within fully differentiated U and L cells of aged colonies. New data from RNA-seq provides both spatial and temporal information on cell metabolic reprogramming during colony ageing and shows that cells at marginal positions are similar to upper cells, but both these cell types are metabolically distinct from cells localized to lower colony regions. As colonies age, dramatic metabolic reprogramming occurs in cells of upper regions, while changes in margin and lower cells are less prominent. Interestingly, whereas clear expression differences were identified between two L cell subpopulations, U cells (which adopt metabolic profiles, similar to those of tumor cells) form a more homogeneous cell population. The data identified crucial metabolic reprogramming events that arise de novo during colony ageing and are linked to U and L cell colony differentiation and support a role for mitochondria in this differentiation process.

scholarly journals Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis

2021 ◽  
Author(s):  
Juliet R. Girard ◽  
Lauren M. Goins ◽  
Dung M. Vuu ◽  
Mark S. Sharpley ◽  
Carrie M. Spratford ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Genetic Dissection ◽  
Rna Seq ◽  
Cell Type ◽  
Biologically Relevant ◽  
Multiple Paths ◽  
Cell Subpopulations ◽  
Smooth Transitions

AbstractMechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single cell RNA-Seq and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, while inhibiting canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.

scholarly journals A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences

2019 ◽  
Author(s):  
Zhisheng Jiang ◽  
Serena Francesca Generoso ◽  
Marta Badia ◽  
Bernhard Payer ◽  
Lucas B. Carey
Keyword(s):  
Cell Lineage ◽  
Gene Expression Signature ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Rna Seq ◽  
Cell Type Specificity ◽  
Expression Signature ◽  
Differentiated Cells ◽  
Different Cell Types ◽  
High Degree

By performing RNA-seq on cells FACS sorted by their proliferation rate, this study identifies a gene expression signature capable of predicting proliferation rates in diverse eukaryotic cell types and species. This signature, applied to scRNAseq data from C.elegans, reveals lineage-specific differences in proliferation during development. In contrast to the universality of the proliferation signature, mitochondria and metabolism related genes show a high degree of cell-type specificity; mouse pluripotent stem cells (mESCs) and differentiated cells (fibroblasts) exhibit opposite relations between mitochondria state and proliferation. Furthermore, we identified a slow proliferating subpopulation of mESCs with higher expression of pluripotency genes. Finally, we show that fast and slow proliferating subpopulations are differentially sensitive to mitochondria inhibitory drugs in different cell types.

scholarly journals SREBP1 regulates mitochondrial metabolism in oncogenic KRAS expressing NSCLC

2020 ◽  
Author(s):  
Christian F. Ruiz ◽  
Emily D. Montal ◽  
John A. Haley ◽  
John D. Haley
Keyword(s):  
De Novo ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Rna Seq ◽  
Small Cell Lung ◽  
Malignant Phenotype ◽  
Transport Chain ◽  
Promote Tumor Growth ◽  
Expression Program

AbstractCancer cells require extensive metabolic reprogramming in order to provide the bioenergetics and macromolecular precursors needed to sustain a malignant phenotype. Mutant KRAS is a driver oncogene that is well known for its ability to regulate the ERK and PI3K signaling pathways. However, it is now appreciated that KRAS can promote tumor growth via upregulation of anabolic metabolism. We recently showed that oncogenic KRAS promotes a gene expression program of de novo lipogenesis in non-small cell lung cancer (NSCLC). To define the mechanism(s) responsible, we focused on the lipogenic transcription factor SREBP1. We observed that KRAS increases SREBP1 expression and genetic knockdown of SREBP1 significantly inhibited cell proliferation of mutant KRAS-expressing cells. Unexpectedly, lipogenesis was not significantly altered in cells subject to SREBP1 knockdown. Carbon tracing metabolic studies showed a significant decrease in oxidative phosphorylation and RNA-seq data revealed a significant decrease in mitochondrial encoded subunits of the electron transport chain (ETC). Taken together, these data support a novel role, distinct from lipogenesis, of SREBP1 on mitochondrial function in mutant KRAS NSCLC.

scholarly journals Mapping the evolving landscape of super-enhancers during cell differentiation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yan Kai ◽  
Bin E. Li ◽  
Ming Zhu ◽  
Grace Y. Li ◽  
Fei Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Target Gene ◽  
Target Genes ◽  
De Novo ◽  
Cell Types ◽  
Functional Enrichment ◽  
Target Gene Expression ◽  
Differentiated Cells ◽  
Super Enhancer

Abstract Background Super-enhancers are clusters of enhancer elements that play critical roles in the maintenance of cell identity. Current investigations on super-enhancers are centered on the established ones in static cell types. How super-enhancers are established during cell differentiation remains obscure. Results Here, by developing an unbiased approach to systematically analyze the evolving landscape of super-enhancers during cell differentiation in multiple lineages, we discover a general trend where super-enhancers emerge through three distinct temporal patterns: conserved, temporally hierarchical, and de novo. The three types of super-enhancers differ further in association patterns in target gene expression, functional enrichment, and 3D chromatin organization, suggesting they may represent distinct structural and functional subtypes. Furthermore, we dissect the enhancer repertoire within temporally hierarchical super-enhancers, and find enhancers that emerge at early and late stages are enriched with distinct transcription factors, suggesting that the temporal order of establishment of elements within super-enhancers may be directed by underlying DNA sequence. CRISPR-mediated deletion of individual enhancers in differentiated cells shows that both the early- and late-emerged enhancers are indispensable for target gene expression, while in undifferentiated cells early enhancers are involved in the regulation of target genes. Conclusions In summary, our analysis highlights the heterogeneity of the super-enhancer population and provides new insights to enhancer functions within super-enhancers.

scholarly journals “De novo Classification of Mouse B Cell Types using Surfaceome Proteotype Maps”

2019 ◽  
Author(s):  
Marc van Oostrum ◽  
Maik Müller ◽  
Fabian Klein ◽  
Roland Bruderer ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
De Novo ◽  
Cell Types ◽  
Glycosylation Sites ◽  
Cell Subpopulations

AbstractSystem-wide quantification of the cell surface proteotype and identification of extracellular glycosylation sites is challenging when sample is limiting. We miniaturized and automated the previously described Cell Surface Capture technology increasing sensitivity, reproducibility, and throughput. We used this technology, which we call autoCSC, to create population-specific surfaceome maps of developing mouse B cells and used targeted flow cytometry to uncover developmental cell subpopulations.

Long Noncoding RNAs in Erythropoiesis and Megakaryopoiesis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2331-2331
Author(s):  
Vikram R Paralkar ◽  
Tejaswini Mishra ◽  
Jing Luan ◽  
Yu Yao ◽  
Neeraja Konuthula ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Noncoding Rnas ◽  
Cell Types ◽  
Long Noncoding Rnas ◽  
Read Length ◽  
Rna Seq ◽  
Erythroid Progenitors ◽  
Specific Expression

Abstract Abstract 2331 Lnc (long noncoding) RNAs are RNA transcripts greater than 200nt that regulate gene expression independent of protein coding potential. It is estimated that thousands of lncRNAs play vital roles in diverse cellular processes and are involved in numerous diseases, including cancer. We hypothesize that multiple lncRNAs regulate erythrocyte and megakaryocyte formation by modulating gene expression. To identify lncRNAs in erythro-megakaryopoiesis, we purified two biological replicates each of murine Ter119+ erythroblasts, CD41+ megakaryocytes and bipotential megakaryocyte-erythroid progenitors (MEPs) [Lin− Kit+, Sca1−, CD16/32−, CD34−]. We performed strand-specific, paired-end, 200nt-read-length deep sequencing (RNA-Seq) to a depth of ∼200 million reads per sample using the Illumina GAII platform. We used the Tophat and Cufflinks suite of bioinformatic tools to assemble and compare de-novo transcriptomes from these three cell types, producing a high-confidence set of 69,488 transcripts. We confirmed that the RNA-seq assemblies accurately reflect gene expression predicted from prior studies. For example, Ter119+ cells were highly enriched for key erythroid transcripts encoding globins, heme synthetic enzymes and specialized membrane proteins. Megakaryocytes expressed high levels of gene encoding lineage-specific integrins and platelet markers. MEPs expressed numerous progenitor genes including Gata2, Kit and Myc. Thus, the RNA-seq data are of high-quality and sufficient complexity to accurately represent erythroid, megakaryocytic and MEP transcriptomes. We used a series of Unix-based bioinformatic filtering tools to identify lncRNAs that are expressed in these transcriptomes. We identified 605 “stringent” lncRNAs, and 813 “potential noncoding” transcripts. 47% of the lncRNAs are novel unannotated transcripts, validating the use of de-novo RNA-Seq in unique cell populations for lncRNA discovery. Among the 605 “stringent” lncRNAs, 103 are erythroid-restricted, 133 are meg-restricted and 280 are MEP-restricted, consistent with reports that lncRNAs exhibit exquisitely cell-type specific expression. Current efforts are aimed at generating a more comprehensive map of lncRNA expression at specific stages of erythroid and megakaryocyte/platelet development, and performing high throughput functional screens to analyze currently identified lncRNAs. Our studies are beginning to define new layers of gene regulation in normal erythro-megakaryopoiesis and are relevant to the pathophysiology of related disorders including various anemias, myeloproliferative and myelodysplastic syndromes and leukemias. Disclosures: No relevant conflicts of interest to declare.

Oestrogen dependence of lactate dehydrogenase and peroxidase in cell subpopulations of 7,12-dimethylbenz[α] anthracene-induced mammary tumours in the rat

1984 ◽  
Vol 101 (1) ◽  
pp. 21-NP
Author(s):  
A. R. Safa ◽  
J. R. Brightwell ◽  
M. T. Tseng
Keyword(s):  
Enzyme Activity ◽  
Lactate Dehydrogenase ◽  
Peroxidase Activity ◽  
Cell Types ◽  
Cell Subpopulation ◽  
Differentiated Cells ◽  
Ldh Activity ◽  
Mammary Tumours ◽  
Multiple Cell ◽  
Cell Subpopulations

ABSTRACT Recent investigations of certain enzymes as markers for predicting the response of breast tumours to hormonal therapy have neglected the possible differential contribution of cell subpopulation(s) within a solid tumour to enzyme activity. In this investigation, lactate dehydrogenase (LDH) and peroxidase activities in density-defined cell subpopulations from autotransplanted 7,12-dimethylbenz[α]anthracene-induced mammary tumours were determined. The effects of ovariectomy and subsequent oestrogen administration on the activity of these enzymes were also examined. Five cell subpopulations (cell bands) were routinely obtained from each mammary tumour. The highest LDH activity was found in cell band 4. The highest level of peroxidase activity was found in cell band 5. These two cell bands with high levels of enzyme activity consisted mainly of poorly differentiated cells. After bilateral ovariectomy, a significant (P < 0·001) decrease in the level of LDH activity in cell bands 3, 4 and 5 was observed. The enzyme activity was reduced to 20, 2·1 and 12% of the preovariectomy levels respectively. Significant (P < 0·05) decreases between baseline and postovariectomy peroxidase values were evident in each cell band. In the presence of oestradiol-17β, significant increases in the LDH activity of band 4 (P < 0·001) and the peroxidase activity of band 5 (P < 0·05) were observed. Our data suggest that, given the existence of multiple cell types in hormone-responsive tumour tissue, the actual cell subpopulation(s) responsible for any enzyme response may be a more precise indicator of hormone dependence. J. Endocr. (1984) 101, 21–26

scholarly journals Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Juliet R Girard ◽  
Lauren M Goins ◽  
Dung M Vuu ◽  
Mark S Sharpley ◽  
Carrie M Spratford ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Genetic Dissection ◽  
Rna Seq ◽  
Cell Type ◽  
Biologically Relevant ◽  
Multiple Paths ◽  
Cell Subpopulations ◽  
Smooth Transitions

Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.

scholarly journals Genetic differences in the histochemically defined structure of oligosaccharides in mice.

1987 ◽  
Vol 35 (11) ◽  
pp. 1231-1244 ◽  
Author(s):  
S S Spicer ◽  
S L Erlandsen ◽  
A C Wilson ◽  
M F Hammer ◽  
R A Hennigar ◽  
...  
Keyword(s):  
Individual Variation ◽  
Cell Types ◽  
Inbred Strains ◽  
Wide Range ◽  
Infiltrating Cells ◽  
Mouse Species ◽  
Homogeneous Cell ◽  
Outbred Strain ◽  
Lymphoid Infiltrates ◽  
Homogeneous Cell Population

A wide range of tissues from three interfertile species of mice and an interspecific hybrid was examined with lectins conjugated to peroxidase to localize specifically glycoconjugates containing terminal alpha-N-acetylgalactosamine, alpha-galactose, and alpha-fucose, and the terminal disaccharide galactose-(beta 1----3)-N-acetylgalactosamine. This battery of lectins disclosed marked heterogeneity of glycoconjugates in different histological sites in a given animal and even between cells in a presumably homogeneous cell population within an organ. No variation with any lectin was observed between individuals of two closely related inbred strains of Mus domesticus at any specific histological or cytological site. In contrast, littermates of an outbred strain of Mus castaneus differed in binding of certain lectins at various sites, attesting to a genetic basis for individual variation. Hybrids between castaneus and domesticus mice also showed individual variation. Moreover, extensive differences between the mouse species were demonstrable with every lectin in glycoconjugates of stored secretions, Golgi cisternae, and apical or basolateral plasmalemma in many cell types. Totaling the differences in tabulated staining intensities for each possible species pair gave a measure of the overall extent of difference at 53 histological sites. According to this measure, the three species are about equally divergent from one another. Some differences between species appeared to depend on histological rather than histochemical variation, as, for example, a greater abundance of granular duct cells in the sublingual and submandibular glands in Mus hortulanus. Other differences were apparently derived from pathological change, as exemplified by casts and lymphoid infiltrates in kidney and structurally atypical submandibular gland lobules in Mus castaneus, and possibly by infiltrating cells in intestinal lamina propria and epithelium in Mus castaneus and hortulanus.

scholarly journals Diverse epithelial cell populations contribute to the regeneration of secretory units in injured salivary glands

Development ◽  
2020 ◽  
Vol 147 (19) ◽  
pp. dev192807
Author(s):  
Ninche Ninche ◽  
Mingyu Kwak ◽  
Soosan Ghazizadeh
Keyword(s):  
Salivary Glands ◽  
De Novo ◽  
Cell Types ◽  
Myoepithelial Cells ◽  
Lineage Tracing ◽  
Secretory Cells ◽  
Cell Populations ◽  
Cellular Plasticity ◽  
Ductal Cells ◽  
Differentiated Cells

ABSTRACTSalivary glands exert exocrine secretory function to provide saliva for lubrication and protection of the oral cavity. Its epithelium consists of several differentiated cell types, including acinar, ductal and myoepithelial cells, that are maintained in a lineage-restricted manner during homeostasis or after mild injuries. Glandular regeneration following a near complete loss of secretory cells, however, may involve cellular plasticity, although the mechanism and extent of such plasticity remain unclear. Here, by combining lineage-tracing experiments with a model of severe glandular injury in the mouse submandibular gland, we show that de novo formation of acini involves induction of cellular plasticity in multiple non-acinar cell populations. Fate-mapping analysis revealed that, although ductal stem cells marked by cytokeratin K14 and Axin2 undergo a multipotency switch, they do not make a significant contribution to acinar regeneration. Intriguingly, more than 80% of regenerated acini derive from differentiated cells, including myoepithelial and ductal cells, that appear to dedifferentiate to a progenitor-like state before re-differentiation into acinar cells. The potential of diverse cell populations serving as a reserve source for acini widens the therapeutic options for hyposalivation.

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