scholarly journals Recent advances in understanding DNA replication: cell type–specific adaptation of the DNA replication program

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1351 ◽  
Author(s):  
Antoine Aze ◽  
Domenico Maiorano
Keyword(s):  
Cell Division ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Genetic Diseases ◽  
Cell Types ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Cell Type Specific ◽  
Division Cell ◽  
Different Cell Types

DNA replication is an essential process occurring prior to cell division. Cell division coupled to proliferation ensures the growth and renewal of a large variety of specialized cell types generated during embryonic development. Changes in the DNA replication program occur during development. Embryonic undifferentiated cells show a high replication rate and fast proliferation, whereas more differentiated cells are characterized by reduced DNA synthesis and a low proliferation rate. Hence, the DNA replication program must adapt to the specific features of cells committed to different fates. Recent findings on DNA synthesis regulation in different cell types open new perspectives for developing efficient and more adapted therapies to treat various diseases such as genetic diseases and cancer. This review will put the emphasis on recent progress made in this field.

DNA Polymerase in Avian Erythroid Cells

1972 ◽  
Vol 11 (3) ◽  
pp. 785-798
Author(s):  
A. F. WILLIAMS
Keyword(s):  
Cell Division ◽  
Dna Synthesis ◽  
Dna Polymerase ◽  
Cell Types ◽  
Polymerase Activity ◽  
Erythroid Cells ◽  
Isolated Nuclei ◽  
Dividing Cells ◽  
Different Cell Types

The level and properties of DNA polymerase activity assayable in extracts of avian erythroid cells was studied. The enzyme was detectable in the dividing cells (erythroblasts) of the erythropoietic series and also the immature non-dividing erythrocytes. It could not be assayed in mature erythrocytes. Investigations showed that activity began to decline at the time of the last cell division of the erythroid series. Properties of the enzyme did change in different cell types; however, the changes did not correlate with cessation of DNA synthesis. Some preliminary results on DNA synthesis by isolated nuclei are also reported and these showed that only nuclei from erythroblasts could synthesize DNA in vitro in the absence of primer.

The Developmental Capacity of Nuclei taken from Intestinal Epithelium Cells of Feeding Tadpoles

Development ◽  
1962 ◽  
Vol 10 (4) ◽  
pp. 622-640 ◽  
Author(s):  
J. B. Gurdon
Keyword(s):  
Genetic Information ◽  
Cellular Differentiation ◽  
Cell Types ◽  
Nuclear Transplantation ◽  
Differentiated Cells ◽  
Developmental Capacity ◽  
Nuclear Changes ◽  
Different Cell Types ◽  
Epithelium Cells ◽  
Saline Medium

An important problem in embryology is whether the differentiation of cells depends upon a stable restriction of the genetic information contained in their nuclei. The technique of nuclear transplantation has shown to what extent the nuclei of differentiating cells can promote the formation of different cell types (e.g. King & Briggs, 1956; Gurdon, 1960c). Yet no experiments have so far been published on the transplantation of nuclei from fully differentiated normal cells. This is partly because it is difficult to obtain meaningful results from such experiments. The small amount of cytoplasm in differentiated cells renders their nuclei susceptible to damage through exposure to the saline medium, and this makes it difficult to assess the significance of the abnormalities resulting from their transplantation. It is, however, very desirable to know the developmental capacity of such nuclei, since any nuclear changes which are necessarily involved in cellular differentiation must have already taken place in cells of this kind.

Changes of the DNA content of differentiating and adult macronuclei of the ciliate Loxodes magnus (Karyorelictida)

1980 ◽  
Vol 44 (1) ◽  
pp. 375-394
Author(s):  
N.N. Bobyleva ◽  
B.N. Kudrjavtsev ◽  
I.B. Raikov
Keyword(s):  
Cell Division ◽  
Dna Replication ◽  
Hydrochloric Acid ◽  
Dna Synthesis ◽  
Acid Hydrolysis ◽  
Gene Amplification ◽  
Dna Content

The DNA content of isolated micronuclei, differentiating macronuclei (macronuclear Anlagen), and adult macronuclei of Loxodes magnus was measured cytofluorimetrically in preparations stained with a Schiff-type reagent, auramine-SO2, following hydrochloric acid hydrolysis. The DNA content of the youngest macronuclear Anlagen proved to be the same as that of telophasic micronuclei (2 c). The Anlagen thus differentiate from micronuclei which are still in G1. The quantity of DNA in the macronuclear Anlagen thereafter rises to the 4-c level, simultaneously with DNA replication in the micronuclei which immediately follows mitosis. In non-dividing animals most micronuclei are already in G2. Adult macronuclei here contain on average 1.5 times more DNA than the micronuclei; their DNA content is about 5–6 c (in some individual nuclei, up to 10 c). These data are consistent with autoradiographic evidence indicating a weak DNA synthesis in the macronuclei of Loxodes and make likely the existence of partial DNA replication (e.g. gene amplification) in the macronuclei. The DNA content of adult macronuclei isolated from dividing animals proved to be significantly smaller than that of macronuclei isolated from non-dividing specimens of the same clone. In 3 clones studied, the former value amounted on average to 71–79, 78 and 95% of the latter, respectively. This drop of DNA content cannot be explained by ‘dilution’ of the old macronuclei with newly formed ones. The quantity of DNA in adult macronuclei thus seems to undergo cyclical changes correlated with cytokinesis, despite the fact that, in Loxodes magnus, the macronuclei themselves never divide and are simply segregated at every cell division. The macronuclei of Loxodes can be termed paradiploid or hyperdiploid.

scholarly journals SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models

2020 ◽  
Author(s):  
Yupeng Wang ◽  
Rosario B. Jaime-Lara ◽  
Abhrarup Roy ◽  
Ying Sun ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Dna Sequences ◽  
Cell Types ◽  
Learning Models ◽  
Cell Type ◽  
Coding Sequences ◽  
Sequence Features ◽  
Cell Type Specific ◽  
Different Cell Types

AbstractWe propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, sequential k-mer (k=5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers including gkm-SVM and DanQ, with regard to distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL is able to directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified according to their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL.

Morphological changes in rat tracheal cells during the adaptive and early growth phase in primary cell culture

1985 ◽  
Vol 74 (1) ◽  
pp. 283-301
Author(s):  
L.Y. Chang ◽  
R. Wu ◽  
P. Nettesheim
Keyword(s):  
Dna Synthesis ◽  
Cell Population ◽  
Growth Phase ◽  
Mucous Cells ◽  
Ciliated Cells ◽  
Differentiated Cells ◽  
Tracheal Cell ◽  
Attached Cell ◽  
Undifferentiated Cells ◽  
Tracheal Epithelial

The purpose of our studies was to determine the fate of different cell types present in early primary cultures of tracheal epithelial cells and, if possible, to elucidate the role they play in the establishment of the cultures. Epithelial cells were isolated from rat tracheas with 0.5% Pronase and were cultured on collagen-coated dishes as described previously. Light and transmission electron microscopic studies showed that the cell population harvested from rat trachea was composed of approximately 30% ciliated cells, 50% granule-containing cells and 20% undifferentiated cells (presumably basal cells). Upon seeding the tracheal cell suspensions into culture, approximately 40% of the cells attached. Cell attachment was virtually complete after 16 h. Roughly 60% of the cells attaching during the first 12 h were neither ciliated nor granulated, suggesting that undifferentiated cells played a major role in establishment of the early cultures. Between 20 and 35% of the cells attaching during this time were identified as granulated cells (mucous cells). Ciliated cells did not start to attach in significant numbers until 8 h after seeding. They never amounted to more than 8–12% of the attached cell population. After 12 h of culture, the cell population underwent a progressive loss of differentiation. The number of poorly differentiated cells (i.e. those showing neither cilia nor mucous granules) increased correspondingly. This loss of differentiation preceded the onset of DNA synthesis and cell growth which began at about 24 and 40 h, respectively. Continuous [3H]thymidine-labelling studies showed that at 48 h after the start of culture about 90% of all attached cells had entered DNA synthesis at least once. This finding is consistent with the interpretation that the ciliated cells are terminally differentiated cells and are probably the only part of the tracheal cell inoculum not participating in the growth of the cultures. At 72 h, the cultures (now in mid-log growth phase) were composed of uniformly undifferentiated cells lacking cilia and mucous granules. The cells nevertheless showed unequivocal epithelial characteristics such as tight junctions and desmosomes. The studies suggest that both basal and mucous cells are responsible for the establishment and growth of the rat tracheal epithelial cell cultures.

scholarly journals Dissecting differential signals in high-throughput data from complex tissues

2019 ◽  
Vol 35 (20) ◽  
pp. 3898-3905 ◽  
Author(s):  
Ziyi Li ◽  
Zhijin Wu ◽  
Peng Jin ◽  
Hao Wu
Keyword(s):  
High Throughput ◽  
Cell Types ◽  
R Package ◽  
Supplementary Information ◽  
Simulation Studies ◽  
Clinical Practices ◽  
High Throughput Data ◽  
Heterogeneous Samples ◽  
Cell Type Specific ◽  
Different Cell Types

Abstract Motivation Samples from clinical practices are often mixtures of different cell types. The high-throughput data obtained from these samples are thus mixed signals. The cell mixture brings complications to data analysis, and will lead to biased results if not properly accounted for. Results We develop a method to model the high-throughput data from mixed, heterogeneous samples, and to detect differential signals. Our method allows flexible statistical inference for detecting a variety of cell-type specific changes. Extensive simulation studies and analyses of two real datasets demonstrate the favorable performance of our proposed method compared with existing ones serving similar purpose. Availability and implementation The proposed method is implemented as an R package and is freely available on GitHub (https://github.com/ziyili20/TOAST). Supplementary information Supplementary data are available at Bioinformatics online.

Stimulation of cell division and DNA replication inPrototheca richardsiby passage through larval amphibian guts

Parasitology ◽  
1993 ◽  
Vol 107 (2) ◽  
pp. 119-124 ◽  
Author(s):  
T. J. C. Beebee ◽  
A. L.-C. Wong
Keyword(s):  
Cell Division ◽  
Dna Replication ◽  
Growth Inhibition ◽  
Dna Synthesis ◽  
Free Living ◽  
Leucine Uptake ◽  
Amphibian Larvae ◽  
Larval Amphibian ◽  
Stimulation Of

SUMMARYPrototheca richardsi, an unpigmented heterotrophic alga, causes growth inhibition in amphibian larvae and has proved refractory to culturein Vitro.P. richardsireplication is dependent on regular passaging through tadpole digestive systems; uptake of thymidine by free-livingProtothecacells and incorporation into DNA are very low by comparison with leucine uptake and incorporation into protein, but DNA synthesis is detectable in cells isolated from tadpole intestines. DNA replication was elicited 6–8 h after ingestion in protothecans fed to tadpoles and subsequently re-isolated from them, providing that the tadpoles were fed subsequent to the ingestion. It appears that passaging through tadpole intestines provides an essential stimulus to maintaining an active cell division cycle inP. richardsi.

scholarly journals Stem-cell-ubiquitous genes spatiotemporally coordinate division through regulation of stem-cell-specific gene networks

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Natalie M. Clark ◽  
Eli Buckner ◽  
Adam P. Fisher ◽  
Emily C. Nelson ◽  
Thomas T. Nguyen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Gene Networks ◽  
Cell Types ◽  
Specific Gene ◽  
Cell Renewal ◽  
Cell Type ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Cell Type Specific ◽  
Stem Cell Type

AbstractStem cells are responsible for generating all of the differentiated cells, tissues, and organs in a multicellular organism and, thus, play a crucial role in cell renewal, regeneration, and organization. A number of stem cell type-specific genes have a known role in stem cell maintenance, identity, and/or division. Yet, how genes expressed across different stem cell types, referred to here as stem-cell-ubiquitous genes, contribute to stem cell regulation is less understood. Here, we find that, in the Arabidopsis root, a stem-cell-ubiquitous gene, TESMIN-LIKE CXC2 (TCX2), controls stem cell division by regulating stem cell-type specific networks. Development of a mathematical model of TCX2 expression allows us to show that TCX2 orchestrates the coordinated division of different stem cell types. Our results highlight that genes expressed across different stem cell types ensure cross-communication among cells, allowing them to divide and develop harmonically together.

scholarly journals Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Lin ◽  
Pawan Noel ◽  
Erkut H. Borazanci ◽  
Jeeyun Lee ◽  
Albert Amini ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Cellular Composition ◽  
Primary Tumors ◽  
Metastatic Lesions ◽  
Tumor Tissues ◽  
Cell Type Specific ◽  
Different Cell Types

Abstract Background Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues. Methods In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets. Results Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival. Conclusions Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.

scholarly journals Cell-type-specific analysis of alternative polyadenylation using single-cell transcriptomics data

2019 ◽  
Vol 47 (19) ◽  
pp. 10027-10039 ◽  
Author(s):  
Eldad David Shulman ◽  
Ran Elkon
Keyword(s):  
Gene Regulation ◽  
Single Cell ◽  
Alternative Polyadenylation ◽  
Cell Types ◽  
Protein Coding ◽  
Multiple Datasets ◽  
Transcriptomics Data ◽  
Cell Type Specific ◽  
Transcriptional Gene Regulation ◽  
Different Cell Types

AbstractAlternative polyadenylation (APA) is emerging as an important layer of gene regulation because the majority of mammalian protein-coding genes contain multiple polyadenylation (pA) sites in their 3′ UTR. By alteration of 3′ UTR length, APA can considerably affect post-transcriptional gene regulation. Yet, our understanding of APA remains rudimentary. Novel single-cell RNA sequencing (scRNA-seq) techniques allow molecular characterization of different cell types to an unprecedented degree. Notably, the most popular scRNA-seq protocols specifically sequence the 3′ end of transcripts. Building on this property, we implemented a method for analysing patterns of APA regulation from such data. Analyzing multiple datasets from diverse tissues, we identified widespread modulation of APA in different cell types resulting in global 3′ UTR shortening/lengthening and enhanced cleavage at intronic pA sites. Our results provide a proof-of-concept demonstration that the huge volume of scRNA-seq data that accumulates in the public domain offers a unique resource for the exploration of APA based on a very broad collection of cell types and biological conditions.

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