scholarly journals Reoccurring neural stem cell divisions in the adult zebrafish telencephalon are sufficient for the emergence of aggregated spatiotemporal patterns

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000708
Author(s):  
Valerio Lupperger ◽  
Carsten Marr ◽  
Prisca Chapouton
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Agent Based ◽  
Brain Hemispheres ◽  
Random Fashion ◽  
Dividing Cells ◽  
Stem Cell Divisions ◽  
Stem Cell Populations

Regulation of quiescence and cell cycle entry is pivotal for the maintenance of stem cell populations. Regulatory mechanisms, however, are poorly understood. In particular, it is unclear how the activity of single stem cells is coordinated within the population or if cells divide in a purely random fashion. We addressed this issue by analyzing division events in an adult neural stem cell (NSC) population of the zebrafish telencephalon. Spatial statistics and mathematical modeling of over 80,000 NSCs in 36 brain hemispheres revealed weakly aggregated, nonrandom division patterns in space and time. Analyzing divisions at 2 time points allowed us to infer cell cycle and S-phase lengths computationally. Interestingly, we observed rapid cell cycle reentries in roughly 15% of newly born NSCs. In agent-based simulations of NSC populations, this redividing activity sufficed to induce aggregated spatiotemporal division patterns that matched the ones observed experimentally. In contrast, omitting redivisions leads to a random spatiotemporal distribution of dividing cells. Spatiotemporal aggregation of dividing stem cells can thus emerge solely from the cells’ history.

scholarly journals Aggregated spatio-temporal division patterns emerge from reoccurring divisions of neural stem cells

2020 ◽  
Author(s):  
V. Lupperger ◽  
C. Marr ◽  
P. Chapouton
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Temporal Distribution ◽  
Adult Neural Stem Cell ◽  
Agent Based ◽  
Random Fashion ◽  
Dividing Cells ◽  
Spatio Temporal ◽  
Stem Cell Populations

AbstractThe regulation of quiescence and cell cycle entry is pivotal for the maintenance of stem cell populations. Regulatory mechanisms however are poorly understood. In particular it is unclear how the activity of single stem cells is coordinated within the population, or if cells divide in a purely random fashion. We addressed this issue by analyzing division events in an adult neural stem cell (NSC) population of the zebrafish telencephalon. Spatial statistics and mathematical modeling of over 80,000 NSCs in 36 brains revealed weakly aggregated, non-random division patterns in space and time. Analyzing divisions at two timepoints allowed us to infer cell cycle and S-phase lengths computationally. Interestingly, we observed rapid cell cycle re-entries in roughly 15% of newly born NSCs. In agent based simulations of NSC populations, this re-dividing activity sufficed to induce aggregated spatio-temporal division patterns that matched the ones observed experimentally. In contrast, omitting re-divisions lead to a random spatio-temporal distribution of dividing cells. Spatio-temporal aggregation of dividing stem cells can thus emerge from the cell’s history, regardless of possible feedback mechanisms in the population.

scholarly journals Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nathan Moore ◽  
Stephen Lyle
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Adult Stem Cells ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Cell Cycle Regulators ◽  
Slow Cycling ◽  
Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

Gene Expression Profiling in Quiescent Stem Cells from Normal and Chronic Myeloid Leukaemia Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2962-2962
Author(s):  
Susan M. Graham ◽  
Gerry J. Graham ◽  
Tessa L. Holyoake
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Stem Cell Marker ◽  
Quiescent Cells ◽  
Dividing Cells ◽  
Quiescent Stem Cells

Abstract Earlier studies have shown that Ph+ quiescent cells exist in chronic myeloid leukaemia (CML) (Blood (1999)94:2056) and we have previously shown that these cells are primitive in that they express the stem cell marker CD34. We have also shown that quiescent CML stem cells are insensitive to the effects of imatinib (IM Novartis Pharma) (Blood (2002) 99:319) and may present a possible source for relapse. This quiescent population therefore represents a potentially significant clinical problem and thus studies aimed at developing methods for eradicating this population are timely. In an effort to identify molecular markers of this population that may allow it to be specifically targeted during therapy, we have set out to investigate the transcriptional differences between quiescent and cycling stem cells. To this end, we have used specific stem cell enrichment and sorting protocols. Leukapheresis products from CML patients (N=5) in chronic phase at diagnosis and mobilised peripheral blood from allogeneic donors (N=3), were selected for CD34+ cells. Hoechst 33342 and Pyronin Y were used to discriminate the quiescent (G0) cells identified as Hoechstlo/Pyroninlo from the cycling cells. In combination with propidium iodide for dead cell exclusion we were able to sort 4–9x105 viable, quiescent stem cells and 4–11x106 cycling cells, which were processed for microarrays. Affymetrix gene chips (U133A) were used for the analysis and the data obtained was analysed using GeneSpring. Number of Genes Changed in Each Comparison 3 Fold 4 Fold 5 Fold CML G0 V CML Div 37 21 10 Norm G0 V Norm Div 188 92 47 CML G0 V Norm G0 168 85 49 CML Div V Norm Div 49 27 8 Initial analysis indicates that the greatest differences in gene expression are between the normal quiescent cells (G0) and normal dividing cells (Div) and between the normal quiescent cells and CML quiescent cells. A large percentage of the genes differentially expressed between the quiescent and cycling normal cells encode regulators of the cell cycle confirming the success of the sorting strategy for quiescent and cycling cells A selection of Genes Up-Regulated in Normal Cycling Cells Compared to G0 Gene Fold Up-regulation PCNA 3 CDC2 8 CCNB2 5 CCN1 3.5 CDC20 6 CDC25A 3.5 MCM5 3 In addition, many of the genes identified in our analysis are consistent with other published expression profiles for haemopoietic cells. Curiously, we have identified unanticipated changes in expression of cell cycle genes in the CML quiescent cells, which merit further investigation. We have also identified a number of unexpected genes as being more than 5 fold changed in the quiescent cells compared to dividing cells for both normal and CML samples. Specifically, there is a large cohort of genes preferentially expressed in quiescent normal or CML cells, which encode members of the chemokine family of proteins. Work is ongoing to establish the relevance, if any, of these genes to stem cell quiescence.

scholarly journals Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis

2016 ◽  
Vol 2016 ◽  
pp. 1-12
Author(s):  
Manish Kurhekar ◽  
Umesh Deshpande
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Deterministic Model ◽  
Model Parameters ◽  
Agent Based Simulation ◽  
Hematopoietic Stem ◽  
Agent Based ◽  
Differentiated Cells ◽  
Stem Cell Populations

Modeling of stem cells not only describes but also predicts how a stem cell’s environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website.

scholarly journals Adult Neurogenesis and the Promise of Adult Neural Stem Cells

2019 ◽  
Vol 13 ◽  
pp. 117906951985687 ◽  
Author(s):  
Hiyaa S Ghosh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Adult Neurogenesis ◽  
Therapeutic Potential ◽  
Precursor Cells ◽  
Adult Brain ◽  
Adult Neural Stem Cell ◽  
Dividing Cells

The adult brain, even though largely postmitotic, is now known to have dividing cells that can make both glia and neurons. Of these, the precursor cells that have the potential to make new neurons in the adult brain have attracted great attention from researchers, anticipating their therapeutic potential for neurodegenerative conditions. In this review, I will focus on adult neurogenesis, from the perspective of the overall neurogenic potential in the adult brain, current understanding of the ‘adult neural stem cell’, and the importance of niche as a decisive factor for neurogenesis under homeostasis and pathologic conditions.

scholarly journals The Effect of Advanced Motherhood on Newborn Offspring’s Hippocampal Neural Stem Cell Proliferation

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Bo Li ◽  
Ping Duan ◽  
Xuefei Han ◽  
Wenhai Yan ◽  
Ying Xing
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Control Group ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Positive Rate ◽  
Mother Group

Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation.Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis.Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres’ diameter was smaller than that of the control group (P<0.05). The EdU positive rate of the old mother group was lower than that of the control group (P<0.05). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (P<0.05). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (P<0.05).Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group.

scholarly journals Cell cycle lengths of stem cells and their lineage from cellular demography

2020 ◽  
Author(s):  
Purna Gadre ◽  
Nitin Nitsure ◽  
Debasmita Mazumdar ◽  
Samir Gupta ◽  
Krishanu Ray
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Fold Increase ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
List Type ◽  
Germline Stem Cells ◽  
Stem Cell Divisions ◽  
Cycle Lengths

AbstractAdult stem cells and their transit-amplifying (TA) progeny dynamically alter their proliferation rates to maintain tissue homeostasis. To test how the division rates of stem cell and TA cells affect tissue growth and differentiation, we developed a computation strategy which estimates the average cell cycle lengths/lifespans of germline stem cells (GSCs) and their TA progeny from cellular demography. Analysis of the wild-type data from Drosophila testis using this method indicated anomalous changes in lifespans during the germline transit-amplification with a nearly 1.3-fold increase after the first division and about a 2-fold decrease in the subsequent stage. Genetic perturbations altering the cell cycle rates of GSC and its immediate daughter, the gonialblast (GB), proportionately changed the rates of subsequent TA divisions. Notably, a nearly 2-fold increase or decrease in the total TA duration did not alter the induction of meiosis after four mitotic cycles. Altogether, these results suggest that the rates of GSC and GB divisions can adjust the rates of subsequent divisions and the onset of differentiation.Significance StatementDynamic regulation of the proliferation rate of stem cells and their transit-amplifying daughters maintains tissue homeostasis in different conditions such as tissue regeneration, aging, and hormonal imbalance. Previous studies suggested that a molecular clock in the stem cell progeny determines the timing of differentiation. This work shows that alterations of the rates of stem cell divisions, as well as that of its progeny, could override the differentiation clock in the Drosophila testis, and highlights a possible mechanism of fine-tuning the transit-amplification program under different conditions such as tissue damage, aging, and hormonal inputs. Also, the method developed for this study could be adapted to estimate lineage expansion plasticity from demographic changes in other systems.HighlightsDetermination of cellular lifespan during transit-amplification from demographyLifespans of Drosophila male germline cells changes anomalously during the TALifespan changes of germline stem cells readjust that of the progeny cellsAnomalous lifespan expansion midway through TA precedes the Bam onset

scholarly journals Cell Cycle Kinetics and Development of Hydra Attenuata

1974 ◽  
Vol 16 (2) ◽  
pp. 359-375 ◽  
Author(s):  
C. N. DAVID ◽  
A. GIERER
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Interstitial Cell ◽  
Flow Model ◽  
Interstitial Cells ◽  
Nerve Cells ◽  
Stem Cell Divisions ◽  
Basal Disk ◽  
Hydra Attenuata

The differentiation of nerve cells and nematocytes in Hydra attenuata has been investigated by labelling interstitial cell precursors with [3H]thymidine and following by autoradiography the appearance of labelled, newly differentiated cells. Nematocyte differentiation occurs only in the gastric region where labelled nematoblasts appear 12 h and labelled nematocytes 72-96 h after addition of [3H]thymidine. Labelled nerves appear in hypostome, gastric region, and basal disk about 18 h after addition of [3H]thymidine. The lag in the appearance of labelled cells includes cell division of the precursor as well as differentiation since nerves and nematocytes have 2n postmitotic nuclear DNA content. A cell flow model is proposed for interstitial cells and their differentiated products. Stem cells occur as single interstitial cells or in pairs. Per cell generation about 60 % of the daughter cells of stem cell divisions remain stem cells and about 40 % differentiate nerves and nematocytes. Nerves differentiate directly from stem cells in about 1 day. Nematocyte differentiation requires 5-7 days including proliferation of a cluster of 4, 8, 16 or 32 interstitial cells and differentiation of a nematocyst capsule in each cell. The numbers of interstitial cells and nematoblasts predicted by the cell flow model from the rates of nerve differentiation (900 nerves/day/ hydra), nematocyte differentiation (1760 nematocyte nests/day/hydra) and stem cell proliferation (stem cell cycle = 24 h), agree with the numbers of these cells observed in hydra. The number of stem cells per hydra is 3000-6000 depending on assumptions about the time of determination. The ratio of nematocyte to nerve differentiation averaged over the whole hydra is 3:1. In the hypostome and basal disk interstitial cell differentiation occurs exclusively to nerve cells while in the gastric region the ratio of nematocyte to nerve differentiation is about 7:1.

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

scholarly journals A hybrid model connecting regulatory interactions with stem cell divisions in the root

2021 ◽  
Vol 2 ◽  
Author(s):  
Lisa Van den Broeck ◽  
Ryan J. Spurney ◽  
Adam P. Fisher ◽  
Michael Schwartz ◽  
Natalie M. Clark ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hybrid Model ◽  
Regulatory Networks ◽  
Quiescent Center ◽  
Specific Expression ◽  
Agent Based ◽  
Cell Divisions ◽  
Cell Type Specific Expression ◽  
Stem Cell Divisions ◽  
Cell Niche

Abstract Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

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