scholarly journals Cell cycle dynamics of human pluripotent stem cells primed for differentiation

2019 ◽  
Author(s):  
Anna Shcherbina ◽  
Jingling Li ◽  
Cyndhavi Narayanan ◽  
William Greenleaf ◽  
Anshul Kundaje ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Expression Patterns ◽  
Human Pluripotent Stem Cells ◽  
Specific Manner ◽  
A Cell ◽  
Cell Cycle Dynamics ◽  
Differentiation Gene ◽  
Cycle Indicator

Understanding the molecular properties of the cell cycle of human pluripotent stem cells (hPSCs) is critical for effectively promoting differentiation. Here, we use the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI) system adapted into hPSCs and perform RNA-sequencing on cell cycle sorted hPSCs primed and unprimed for differentiation. Gene expression patterns of signaling factors and developmental regulators change in a cell cycle-specific manner in cells primed for differentiation without altering genes associated with pluripotency. Furthermore, we identify an important role for PI3K signaling in regulating the early transitory states of hPSCs towards differentiation.

scholarly journals Brief Report: Cell Cycle Dynamics of Human Pluripotent Stem Cells Primed for Differentiation

Stem Cells ◽  
2019 ◽  
Vol 37 (9) ◽  
pp. 1151-1157 ◽  
Author(s):  
Anna Shcherbina ◽  
Jingling Li ◽  
Cyndhavi Narayanan ◽  
William Greenleaf ◽  
Anshul Kundaje ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Cell Cycle Dynamics

scholarly journals A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation

2015 ◽  
Vol 210 (7) ◽  
pp. 1257-1268 ◽  
Author(s):  
Sundari Chetty ◽  
Elise N. Engquist ◽  
Elie Mehanna ◽  
Kathy O. Lui ◽  
Alexander M. Tsankov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Differentiation Potential ◽  
Germ Layers ◽  
Positive Effects ◽  
Src Inhibitor ◽  
Expression Of Genes

Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation.

scholarly journals A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation

2015 ◽  
Vol 212 (11) ◽  
pp. 21211OIA91 ◽  
Author(s):  
Sundari Chetty ◽  
Elise Engquist ◽  
Elie Mehanna ◽  
Kathy Lui ◽  
Alexander Tsankov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Src Inhibitor

scholarly journals Establish deeper understanding on the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detail analyses

2020 ◽  
Author(s):  
Ping Zhou ◽  
Jia-Min Shi ◽  
Jing-E Song ◽  
Yu Han ◽  
Hong-Jiao Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Pluripotent Stem Cells ◽  
Telomerase Activity ◽  
Human Pluripotent Stem Cells ◽  
Cell Counting ◽  
Integrated Analysis ◽  
Differentiation Process ◽  
Cell Type

Abstract Background: Derivation of the osteoblast-like cell from human pluripotent stem cell becomes a hot topic in bone tissue engineering. Although many improvements have been achieved in this field, low induction efficiency because of the non-directed differentiation process hampers their application in bone regeneration. We think lack of detailed understanding on the osteogenic differentiation process should be the main reason.Methods: Monolayer cultured human embryonic stem cells and human induced pluripotent stem cells were inducted in traditional serum-containing osteogenic medium for 35 days. Except for traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied cell counting, cell telomerase activity, cell cycle and quantitative expression of runt-related transcription factor 2 as essential indicators to analyze the cell type changes during the differentiation process. Results: The population of differentiated cells are quite heterogenous throughout 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type changes and tumorigenicity of obtained cells. Moreover, nuclear staining should be a recommended method to evaluate the cell number, because, it is still a great challenge to dissociate cells with varying differentiation times into single cells with high survival rate. Finally, a dynamic map was made to integrated analysis of these results, and the cell types at defined stages of osteogenic differentiation of human pluripotent stem cells was concluded. Conclusions: This study lay foundation to improve the in vitro osteogenic differentiation efficiency of human pluripotent stem cells by supplementing functional compounds at each stage according to a time-frame, then establish a step-wised induction system in the future.

RELB Alters Proliferation of Human Pluripotent Stem Cells via IMP3- and LIN28-Mediated Modulation of the Expression of IGF2 and Other Cell-Cycle Regulators

2015 ◽  
Vol 24 (16) ◽  
pp. 1888-1900 ◽  
Author(s):  
Nilay Yogeshkumar Thakar ◽  
Dmitry Alexander Ovchinnikov ◽  
Marcus Lachlan Hastie ◽  
Jeffrey Gorman ◽  
Ernst Jurgen Wolvetang
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Cell Cycle Regulators

scholarly journals TDG regulates cell cycle progression in human neural progenitors

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 497
Author(s):  
Igal Germanguz ◽  
Jenny C. Park ◽  
Jessica Cinkornpumin ◽  
Aryeh Solomon ◽  
Minori Ohashi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Methylation Status ◽  
Human Pluripotent Stem Cells ◽  
Dna Demethylation ◽  
Neural Progenitors ◽  
Specific Cell ◽  
Active Demethylation

Background: As cells divide, they must both replicate their DNA and generate a new set of histone proteins.  The newly synthesized daughter strands and histones are unmodified, and must therefore be covalently modified to allow for transmission of important epigenetic marks to daughter cells.  Human pluripotent stem cells (hPSCs) display a unique cell cycle profile, and control of the cell cycle is known to be critical for their proper differentiation and survival.  A major unresolved question is how hPSCs regulate their DNA methylation status through the cell cycle, namely how passive and active demethylation work to maintain a stable genome. Thymine-DNA glycosylase (TDG), an embryonic essential gene, has been recently implicated as a major enzyme involved in demethylation. Methods: We use human pluripotent stem cells and their derivatives to investigate the role of TDG in differentiation and proliferation.  To perform loss of function of TDG, RNA Interference was used.  To study the cell cyle, we engineered human pluripotent stem cells to express the FUCCI tool which marks cells at various stages of the cell cycle with distinct patterns of fluorescent proteins.  We also used cell cycle profiling by FACS, and DNA methylation analysis to probe a connection between DNA demethylation and cell cycle. Results: Here we present data showing that TDG regulates cell cycle dynamics in human neural progenitors (NPCs) derived from hPSCs, leading to changes in  cell cycle related gene expression and neural differentiation capacity.  These data show that loss of TDG function can block differentiation by driving proliferation of neural progenitors.  We also identify specific cell cycle related genes whose expression changes upon loss of TDG expression. Conclusions: These observations suggest that TDG and active demethylation play an important role in hPSC cell cycle regulation and differentiation.

scholarly journals Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells

2021 ◽  
Vol 17 (3) ◽  
pp. e1008778
Author(s):  
Jared Brown ◽  
Christopher Barry ◽  
Matthew T. Schmitz ◽  
Cara Argus ◽  
Jennifer M. Bolin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Cultures ◽  
Pluripotent Stem Cells ◽  
Time Course ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Human Pluripotent Stem Cells

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.

scholarly journals MicroRNA miR-302 Inhibits the Tumorigenecity of Human Pluripotent Stem Cells by Coordinate Suppression of the CDK2 and CDK4/6 Cell Cycle Pathways

2010 ◽  
Vol 70 (22) ◽  
pp. 9473-9482 ◽  
Author(s):  
Shi-Lung Lin ◽  
Donald C. Chang ◽  
Shao-Yao Ying ◽  
Davey Leu ◽  
David T.S. Wu
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells
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