scholarly journals Wnt Signaling and Its Impact on Mitochondrial and Cell Cycle Dynamics in Pluripotent Stem Cells

Genes ◽  
2018 ◽  
Vol 9 (2) ◽  
pp. 109 ◽  
Author(s):  
Megan Rasmussen ◽  
Natalya Ortolano ◽  
Alejandra Romero-Morales ◽  
Vivian Gama
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Wnt Signaling ◽  
Pluripotent Stem Cells ◽  
Cell Cycle Dynamics

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

Abstract 41: Cell Cycle Activation of Cardiomyocytes Derived From Induced Pluripotent Stem Cells for Cardiac Regeneration

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Wuqiang Zhu ◽  
Meng Zhao ◽  
Saidulu Mattapally ◽  
Ling Gao ◽  
Jianyi Zhang
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cardiac Function ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Mass ◽  
Brdu Incorporation ◽  
Myocardial Repair ◽  
Cyclin D2 ◽  
Induced Pluripotent

Transplantation of cardiomyocytes derived from induced pluripotent stem cells (iPSCs) improves cardiac function in animal models with myocardial infarction. However, the poor number of survived cells and the low proliferation capability of cardiomyocyte derived from iPSCs are bottlenecks in myocardial repair with cell therapy. We hypothesize that increasing the number of surviving iPSC-CMs in the engraftment via cell cycle induction may lead to a transmural replacement of scar tissue and a lasting restoration of cardiac function. Cyclin D2 is a protein that regulates cell cycle transition from G1 to S phase. We transfected MHC-cyclin D2 (designated as MHC-cycD2) cDNA into the iPSCs, and differentiated the iPSCs into cardiomyocytes. Comparing to non-expressing cells, MHC-cycD2-expressing cardiomyocytes displayed increased Brdu incorporation activity, suggesting the enhanced cell cycle in MHC-cycD2-expressing cardiomyocytes. Cell cycle activity was confirmed by increased number of Ki-67 and PCNA positive immunostaining cardiomyocytes and more contractile embryonic body cell mass in MHC-cycD2-expressing culture compared to non-expressing culture. Data from Q-PCR and histology suggested that expression of MHC-cycD2 didn’t alter the pluripotency or cardiomyogenic potential of iPSCs. Thus, we have successfully induced cell cycle in iPSC-derived cardiomyocytes via expression of cyclin D2. We are currently studying if MHC-cycD2-expressing iPSC-cardiomyocytes exhibit superior regenerative potential compared to their non-expressing counterparts following transplantation into chronically infarcted hearts.

scholarly journals Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

2021 ◽  
Vol 118 (34) ◽  
pp. e2108145118
Author(s):  
Anja Bufe ◽  
Ana García del Arco ◽  
Magdalena Hennecke ◽  
Anchel de Jaime-Soguero ◽  
Matthias Ostermaier ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Wnt Signaling ◽  
Pluripotent Stem Cells ◽  
Target Genes ◽  
Genome Maintenance ◽  
Spindle Poles ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Canonical Wnt

Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating β-catenin target genes. Recent evidence showed that β-catenin–independent Wnt signaling is also required for faithful execution of mitosis. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during cell division. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization at the spindle. Accordingly, inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. We propose that Wnt signaling monitors KIF2A activity at the spindle poles during mitosis to ensure timely chromosome alignment. Our findings highlight a function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.

scholarly journals The Wnt Signaling Inhibitor Dickkopf-1 Is Required for Reentry into the Cell Cycle of Human Adult Stem Cells from Bone Marrow

2003 ◽  
Vol 278 (30) ◽  
pp. 28067-28078 ◽  
Author(s):  
Carl A. Gregory ◽  
Harpreet Singh ◽  
Anthony S. Perry ◽  
Darwin J. Prockop
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Wnt Signaling ◽  
Adult Stem Cells ◽  
Human Adult ◽  
Dickkopf 1

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.

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