Single-cell approaches to understand genome organisation throughout the cell cycle

2019 ◽  
Vol 63 (2) ◽  
pp. 209-216
Author(s):  
Sarah E. McClelland
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Biological Data ◽  
Genome Architecture ◽  
Chromosome Architecture ◽  
Current State ◽  
Topologically Associated Domains ◽  
Mammalian Genomes ◽  
A Cell ◽  
Cell Variation

Abstract Mammalian genomes are ordered at several scales, ranging from nucleosomes (beads on a string), to topologically associated domains (TADs), laminar associated domains (LADs), and chromosome territories. These are described briefly below and we refer the reader to some recent comprehensive reviews on genome architecture summarising the current state of knowledge of the organisational principles of the nucleus [1,2]. Biological observations from populations of millions of individual cells can reveal consensus behaviour. New methods to study and interpret biological data at the single-cell level have recently been instrumental in revealing new understanding of cell-to-cell variation and novel biology. Here we will summarise the recent advances in single-cell technology that have provided insights into the behaviour of the mammalian genome during a cell cycle. We will focus on the interphase domain structure of chromosomes, including TADs and LADs, and how chromosome architecture changes during the cell cycle. The role of genome architecture relating to gene expression has been reviewed elsewhere [3].

scholarly journals Kronos scRT: a uniform framework for single-cell replication timing analysis

2021 ◽  
Author(s):  
Stefano Gnan ◽  
Joseph M. Josephides ◽  
Xia Wu ◽  
Manuela Spagnuolo ◽  
Dalila Saulebekova ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Sorting ◽  
Timing Analysis ◽  
Replication Timing ◽  
Genomic Region ◽  
Cell Replication ◽  
Specific Order ◽  
Mammalian Genomes ◽  
A Cell ◽  
Cell Type Specific

Mammalian genomes are replicated in a cell-type specific order and in coordination with transcription and chromatin organization. Although the field of replication is also entering the single-cell era, current studies require cell sorting, individual cell processing and have yielded a limited number (<100) of cells. Here, we have developed Kronos scRT (https://github.com/CL-CHEN-Lab/Kronos scRT), a software for single-cell Replication Timing (scRT) analysis. Kronos scRT does not require a specific platform nor cell sorting, allowing the investigation of large datasets obtained from asynchronous cells. Analysis of published available data and droplet-based scWGS data generated in the current study, allows exploitation of scRT data from thousands of cells for different mouse and human cell lines. Our results demonstrate that, although most cells replicate within a close timing range for a given genomic region, replication can also occur stochastically throughout S phase. Altogether, Kronos scRT allows investigating the RT program at a single-cell resolution for both homogeneous and heterogeneous cell populations in a fast and comprehensive manner.

scholarly journals Functional oscillation of a multienzyme glucosome assembly during cell cycle progression

2022 ◽  
Author(s):  
Miji Jeon ◽  
Danielle L Schmitt ◽  
Minjoung Kyoung ◽  
Songon An
Keyword(s):  
Cell Cycle ◽  
Glucose Metabolism ◽  
Single Cell ◽  
Cell Biology ◽  
Cell Cycle Progression ◽  
Metabolic Adaptation ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Size Dependent ◽  
A Cell

Glucose metabolism has been studied extensively to understand functional interplays between metabolism and a cell cycle. However, our understanding of cell cycle-dependent metabolic adaptation particularly in human cells remains largely elusive. Meanwhile, human enzymes in glucose metabolism are shown to functionally organize into three different sizes of a multienzyme metabolic assembly, the glucosome, to regulate glucose flux in a size-dependent manner. Here, using fluorescence single-cell imaging techniques, we discover that glucosomes spatiotemporally oscillate during a cell cycle in an assembly size-dependent manner. Importantly, their oscillation at single-cell levels is in accordance with functional contributions of glucose metabolism to cell cycle progression at a population level. Collectively, we demonstrate functional oscillation of glucosomes during cell cycle progression and thus their biological significance to human cell biology.

scholarly journals Concurrent processes setE. colicell division

2018 ◽  
Vol 4 (11) ◽  
pp. eaau3324 ◽  
Author(s):  
Gabriele Micali ◽  
Jacopo Grilli ◽  
Matteo Osella ◽  
Marco Cosentino Lagomarsino
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Single Cell ◽  
Chromosome Segregation ◽  
Genetic Material ◽  
Replication Initiation ◽  
Concurrent Processes ◽  
A Cell ◽  
Rate Limiting ◽  
Cell Data

A cell can divide only upon completion of chromosome segregation; otherwise, its daughters would lose genetic material. However, we do not know whether the partitioning of chromosomes is the key event for the decision to divide. We show how key trends in single-cell data reject the classic idea of replication-segregation as the rate-limiting process for cell division. Instead, the data agree with a model where two concurrent processes (setting replication initiation and interdivision time) set cell division on competing time scales. During each cell cycle, division is set by the slowest process (an “AND” gate). The concept of transitions between cell cycle stages as decisional processes integrating multiple inputs instead of cascading from orchestrated steps can affect the way we think of the cell cycle in general.

scholarly journals The Less Known Cyclins—Uncovered

2021 ◽  
Vol 11 (5) ◽  
pp. 2320
Author(s):  
Agnieszka Żuryń ◽  
Aleksandra Opacka ◽  
Adrian Krajewski ◽  
Wioletta Zielińska ◽  
Alina Grzanka
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Differentiation ◽  
Cancer Cells ◽  
Present Report ◽  
Life Stage ◽  
Cyclin Dependent Kinases ◽  
Current State ◽  
Different Types ◽  
A Cell

Cyclins belong to a group of proteins that are cyclically produced and destructed in a cell. Cyclins are a family of proteins that are a key component of the cell cycle regulating system, which level of expression depends on the phase of the cycle. Cyclins regulate the activity of cyclin-dependent kinases (Cdk), thanks to which they influence the length of individual phases of the cell cycle and also determine whether the cell can enter the next life stage. Proper expression of cyclins plays an important role in processes such as proliferation, transcription, DNA repair and cell differentiation. However, dysregulation of their expression is one of the most important disorders leading to the development of different types of cancer, which suggests that cyclins can be defined as a prognostic marker. Currently, we may distinguish >10 members of the cyclins family participating in the division of human cells. The group of less known cyclins includes C, F, G, H, I, J, K, L, M, O, T and Y cyclins. The present report demonstrates the current state of knowledge considering less known cyclins and their role in normal and cancer cells.

scholarly journals Single-cell absolute contact probability detection reveals that chromosomes are organized by multiple, low-frequency yet specific interactions

2017 ◽  
Author(s):  
Diego I. Cattoni ◽  
Andrés M. Cardozo Gizzi ◽  
Mariya Georgieva ◽  
Marco Di Stefano ◽  
Alessandro Valeri ◽  
...  
Keyword(s):  
Single Cell ◽  
Low Frequency ◽  
Super Resolution ◽  
Specific Interactions ◽  
Chromosome Architecture ◽  
Dna Labeling ◽  
Topologically Associated Domains ◽  
Large Heterogeneity ◽  
Transcriptional State ◽  
Eukaryotic Genomes

AbstractAt the kilo- to mega-base pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combined high-content super-resolution microscopies with state-of-the-art DNA labeling methods to reveal the variability in the multiscale organization of the Drosophila genome. We found that association frequencies within TADs and between TAD borders are below ~10%, independently of TAD size, epigenetic state, or cell type. Critically, despite this large heterogeneity, we were able to visualize nanometer-sized epigenetic domains at the single-cell level. In addition, absolute contact frequencies within and between TADs were to a large extent defined by genomic distance, higher-order chromosome architecture, and epigenetic identity. We propose that TADs and compartments are organized by multiple, small frequency, yet specific interactions that are regulated by epigenetics and transcriptional state.

scholarly journals pcnaDeep: A Fast and Robust Single-Cell Tracking Method Using Deep-Learning Mediated Cell Cycle Profiling

2021 ◽  
Author(s):  
Yifan Gui ◽  
Shuang Shuang Xie ◽  
Yanan Wang ◽  
Ping Wang ◽  
Renzhi Yao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Deep Learning ◽  
Single Cell ◽  
Cell Tracking ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Time Lapse ◽  
Molecular Control ◽  
A Cell ◽  
User Friendly

Motivation: Computational methods that track single-cells and quantify fluorescent biosensors in time-lapse microscopy images have revolutionised our approach in studying the molecular control of cellular decisions. One barrier that limits the adoption of single-cell analysis in biomedical research is the lack of efficient methods to robustly track single-cells over cell division events. Results: Here, we developed an application that automatically tracks and assigns mother-daughter relationships of single-cells. By incorporating cell cycle information from a well-established fluorescent cell cycle reporter, we associate mitosis relationships enabling high fidelity long-term single-cell tracking. This was achieved by integrating a deep-learning based fluorescent PCNA signal instance segmentation module with a cell tracking and cell cycle resolving pipeline. The application offers a user-friendly interface and extensible APIs for customized cell cycle analysis and manual correction for various imaging configurations. Availability and Implementation: pcnaDeep is an open-source Python application under the Apache 2.0 licence. The source code, documentation and tutorials are available at https://github.com/chan-labsite/PCNAdeep.

Apicobasal polarity and cell proliferation during development

2012 ◽  
Vol 53 ◽  
pp. 95-109 ◽  
Author(s):  
Nitin Sabherwal ◽  
Nancy Papalopulu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Polarity ◽  
Cross Talk ◽  
Polarization State ◽  
Cell Polarization ◽  
Cellular Processes ◽  
Current State ◽  
Apicobasal Polarity ◽  
A Cell

Cell polarization and cell division are two fundamental cellular processes. The mechanisms that establish and maintain cell polarity and the mechanisms by which cells progress through the cell cycle are now fairly well understood following decades of experimental work. There is also increasing evidence that the polarization state of a cell affects its proliferative properties. The challenge now is to understand how these two phenomena are mechanistically connected. The aim of the present chapter is to provide an overview of the evidence of cross-talk between apicobasal polarity and proliferation, and the current state of knowledge of the precise mechanism by which this cross-talk is achieved.

Single cell RNA-Seq of hematopoietic stem cells reveals a cell cycle-dependent interplay between aging and differentiation

2014 ◽  
Vol 42 (8) ◽  
pp. S21
Author(s):  
Monika Kowalczyk ◽  
Itay Tirosh ◽  
Dirk Heckl ◽  
Benjamin Ebert ◽  
Aviv Regev
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Rna Seq ◽  
Hematopoietic Stem ◽  
A Cell ◽  
Cycle Dependent

scholarly journals Esrrb is a cell cycle dependent priming factor balancing between pluripotency and differentiation

2020 ◽  
Author(s):  
Sapir Herchcovici Levi ◽  
Lee Arnon ◽  
Sharon Feldman ◽  
Adi Alajem ◽  
Danny Bavli ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Retinoic Acid ◽  
Single Cell ◽  
Embryonic Stem ◽  
Dependent Manner ◽  
Reporter System ◽  
Functional Link ◽  
A Cell ◽  
Cycle Dependent

AbstractCell cycle and differentiation decisions are tightly linked; however, the underlying principles that drive these decisions are not fully understood. Here, we combined cell-cycle reporter system and single-cell RNA-seq profiling to study the transcriptomes of mouse embryonic stem cells (ESCs) in the context of cell cycle states and differentiation. By applying a retinoic acid-based protocol as a differentiation assay representing exit from pluripotency, we show that Esrrb, a key pluripotent factor is upregulated during G2/M phase and promptly downregulated during exit from pluripotency. Enhancer chromatin states and Esrrb ChIP-seq map expose Esrrb’s association with differentiation genes, were in the context of retinoic acid, enhancers associated with differentiation program driving extraembryonic endoderm cells (XENs). We show that only G2/M ESCs were capable of differentiating into XENs, whereas cells in the G1 phase predominantly produce epiblast stem cells (EpiSCs). Furthermore, Cells engineered to overexpress Esrrb allowed G1 ESCs to produce XENs, while Esrrb knockout ESCs completely lost their potential to differentiate into XEN. Interestingly, this phenomenon is unique to the pluripotency state as sorting cells after initiation of differentiation resulted in a cell cycle-independent differentiation decisions. Cells in both G1 and G2/M phases contributed equally to EpiSC and XEN cellular lineages. Taken together, this study reveals an important functional link between Esrrb and cell-cycle states during exit from pluripotency. Our novel approach of applying single cell RNAseq in a cell cycle dependent manner can be further expand into other differentiation assays and expand our understanding of early differentiation events.

357: Interstitial Cystitis Anti-Proliferative Factor (APF) as a Cell-Cycle Modulator

2004 ◽  
Vol 171 (4S) ◽  
pp. 93-94
Author(s):  
Hani Rashid ◽  
Susan Keay ◽  
Chen-Ou Zhang ◽  
Edward M. Messing ◽  
Jay Reeder
Keyword(s):  
Cell Cycle ◽  
Interstitial Cystitis ◽  
A Cell
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