scholarly journals Non-cell-autonomous promotion of pluripotency induction mediated by YAP

2018 ◽  
Author(s):  
Amaleah Hartman ◽  
Xiao Hu ◽  
Xinyue Chen ◽  
Anna E. Eastman ◽  
Cindy Yang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Matricellular Proteins ◽  
Fate Control ◽  
Promotional Effect ◽  
Cellular Context ◽  
Opposing Effects ◽  
Cell Fate Control ◽  
Heterologous Cell

SUMMARYWhile Yes-associated protein (YAP) antagonizes pluripotency during early embryogenesis, it has also been shown to promote stemness of multiple stem cell types, including pluripotent stem cells. Whether cellular context underlies these distinct functions of YAP in pluripotency remains unclear. Here, we establish that depending on the specific cells in which it is expressed, YAP exhibits opposing effects on pluripotency induction from somatic cells. Specifically, YAP inhibits pluripotency induction cell-autonomously but promotes it non-cell-autonomously. For its non-cell-autonomous role, YAP alters the expression of many secreted and matricellular proteins including CYR61, which recapitulates the promotional effect when added as a recombinant protein. Thus, we define a unique YAP-driven non-cell-autonomous process that enhances pluripotency induction. Our work highlights the importance of considering the distinct contributions from heterologous cell types in deciphering the mechanism of cell fate control and calls for careful re-examination of the co-existing bystander cells in complex cultures or tissues.

scholarly journals Visualizing Cell Cycle Phase Organization and Control During Neural Lineage Elaboration

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2112
Author(s):  
Fatma Rabia Urun ◽  
Adrian W Moore
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Types ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cell Cycle Regulators ◽  
Neural Lineage ◽  
Fate Control ◽  
A Cell ◽  
Cell Fate Control

In neural precursors, cell cycle regulators simultaneously control both progression through the cell cycle and the probability of a cell fate switch. Precursors act in lineages, where they transition through a series of cell types, each of which has a unique molecular identity and cellular behavior. Thus, investigating links between cell cycle and cell fate control requires simultaneous identification of precursor type and cell cycle phase, as well as an ability to read out additional regulatory factor expression or activity. We use a combined FUCCI-EdU labelling protocol to do this, and then apply it to the embryonic olfactory neural lineage, in which the spatial position of a cell correlates with its precursor identity. Using this integrated model, we find the CDKi p27KIP1 has different regulation relative to cell cycle phase in neural stem cells versus intermediate precursors. In addition, Hes1, which is the principle transcriptional driver of neural stem cell self-renewal, surprisingly does not regulate p27KIP1 in this cell type. Rather, Hes1 indirectly represses p27KIP1 levels in the intermediate precursor cells downstream in the lineage. Overall, the experimental model described here enables investigation of cell cycle and cell fate control linkage from a single precursor through to a lineage systems level.

Advances and Challenges in Kidney Organoids

2021 ◽  
Vol 16 ◽  
Author(s):  
Vikram Sabapathy ◽  
Gabrielle Costlow ◽  
Rajkumar Venkatadri ◽  
Murat Dogan ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Complex Structures ◽  
Cell Culture Systems ◽  
Epigenetic Signatures ◽  
Kidney Organoids

: The advent of organoids has renewed researcher's interest in in vitro cell culture systems. A wide variety of protocols, primarily utilizing pluripotent stem cells, are under development to improve organoid generation to mimic organ development. The complexity of organoids generated is greatly influenced based on the method used. Understanding the process of kidney organoid formation gives developmental insights into how renal cells form, mature, and interact with the adjacent cells to form specific spatiotemporal structural patterns. This knowledge can bridge the gaps in understanding in vivo renal developmental processes. Evaluating genetic and epigenetic signatures in specialized cell types can help interpret the molecular mechanisms governing cell fate. In addition, development in single-cell RNA sequencing and 3D bioprinting and microfluidic technologies has led to better identification and understanding of a variety of cell types during differentiation and designing of complex structures to mimic the conditions in vivo. While several reviews have highlighted the application of kidney organoids, there is no comprehensive review of various methodologies specifically focusing on the kidney organoids. This review summarizes the updated differentiation methodologies, applications, and challenges associated with kidney organoids. Here we have comprehensively collated all the different variables influencing the organoid generation.

Neural Stem Cell Fate Control on Micropatterned Substrates

2017 ◽  
pp. 19-44 ◽  
Author(s):  
Leonora Buzanska ◽  
Marzena Zychowicz ◽  
Ana Ruiz ◽  
François Rossi
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Stem Cell Fate ◽  
Fate Control ◽  
Cell Fate Control

scholarly journals The histone demethylase UTX enables RB-dependent cell fate control

2010 ◽  
Vol 24 (4) ◽  
pp. 327-332 ◽  
Author(s):  
J. K. Wang ◽  
M.-C. Tsai ◽  
G. Poulin ◽  
A. S. Adler ◽  
S. Chen ◽  
...  
Keyword(s):  
Cell Fate ◽  
Histone Demethylase ◽  
Fate Control ◽  
Dependent Cell ◽  
Cell Fate Control

Ping-pong cell-fate control

2004 ◽  
Vol 2 (10) ◽  
pp. 771-771
Author(s):  
Susan Jones
Keyword(s):  
Cell Fate ◽  
Fate Control ◽  
Ping Pong ◽  
Cell Fate Control

scholarly journals DNA damage strength modulates a bimodal switch of p53 dynamics for cell-fate control

BMC Biology ◽  
2013 ◽  
Vol 11 (1) ◽  
pp. 73 ◽  
Author(s):  
Xi Chen ◽  
Jia Chen ◽  
Siting Gan ◽  
Huaji Guan ◽  
Yuan Zhou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Fate Control ◽  
Cell Fate Control

scholarly journals Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

2019 ◽  
Author(s):  
Coral K. Wille ◽  
Rupa Sridharan
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Transcriptional Elongation ◽  
Mrna Levels ◽  
Mesenchymal To Epithelial Transition ◽  
Ipsc Generation ◽  
Induced Pluripotent

ABSTRACTThe ability of pluripotent stem cells to be poised to differentiate into any somatic cell type is partly derived from a unique chromatin structure that is depleted for transcriptional elongation associated epigenetic modifications, primarily H3K79 methylation. Inhibiting the H3K79 methyltransferase, Dot1L, increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs) most potently at the mid-point of the process. Surprisingly, despite the enrichment of H3K79me2 on thousands of actively transcribed genes, Dot1L inhibition (Dot1Li) results in few changes in steady state mRNA levels during reprogramming. Dot1Li spuriously upregulates genes not involved in pluripotency and does not shutdown the somatic program. Depletion of the few genes that are downregulated, such as Nfix, enhances reprogramming efficiency in cooperation with Dot1Li. Contrary to the prevalent view, Dot1Li promotes iPSC generation beyond early phases of reprogramming such as the mesenchymal to epithelial transition and from already epithelial cell types including keratinocytes. Significantly, Dot1L inhibition does not enhance lineage conversion to neurons or muscle cells. Taken together, our results indicate that H3K79me is not a universal barrier of cell fate transitions but specifically protects somatic cells from reverting to the pluripotent state.

scholarly journals ANALYSIS OF INTRACELLULAR SIGNALING KINETICS PREDICTS PRESENTATION MODES AND TARGETS FOR STEM CELL FATE CONTROL

2005 ◽  
Vol preprint (2007) ◽  
pp. e130
Author(s):  
Alborz Mahdavi ◽  
Ryan E Davey ◽  
Patrick Bhola ◽  
Ting Yin ◽  
Peter W Zandstra
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Intracellular Signaling ◽  
Stem Cell Fate ◽  
Fate Control ◽  
Presentation Modes ◽  
Cell Fate Control
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