scholarly journals Lineages of embryonic stem cells show non-Markovian state transitions

2020 ◽  
Author(s):  
Tee Udomlumleart ◽  
Sofia Hu ◽  
Salil Garg
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Developmental State ◽  
Markovian Process ◽  
State Transitions ◽  
Informational Entropy ◽  
Kin Relations ◽  
State Switching

AbstractPluripotent embryonic stem cells (ESCs) contain the ability to constitute the cell types of the adult vertebrate through a series of developmental state transitions. In culture, ESCs reversibly transition between states in a manner previously described as stochastic. However, whether ESCs retain memory of their previous states or transition in a memoryless (Markovian) process remains relatively unknown. Here we show lineages of ESCs do not exhibit the Markovian property: their previous states and kin relations influence future choices. In a subset of lineages, related ESCs remain likely to occupy the same state weeks after labeling. Unexpectedly, the distribution of lineages across states away from the equilibrium point predicted by a Markov model remains consistent over time, suggesting a conservation of informational entropy in this system. Additionally, some lineages appear highly dynamic in their ability to switch states but do not dominate the culture, suggesting that state switching is a separable property from growth. Together, these data suggest ESC state transitions are a proscribed process governed by additional variables.

scholarly journals A mini review on production of pluripotency factors (Oct4, Sox2, Klf4 and c-Myc) through recombinant protein technology

2020 ◽  
Vol 5 (1) ◽  
pp. 1-4 ◽  
Author(s):  
David Septian Sumanto Marpaung ◽  
Ayu Oshin Yap Sinaga
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Cell Types ◽  
Induced Pluripotency ◽  
Pluripotency Factors ◽  
Induced Pluripotent

The four transcription factors OCT4, SOX2, KLF4 and c-MYC are highly expressed in embryonic stem cells (ESC) and their overexpression can induce pluripotency, the ability to differentiate into all cell types of an organism. The ectopic expression such transcription factors could reprogram somatic stem cells become induced pluripotency stem cells (iPSC), an embryonic stem cells-like. Production of recombinant pluripotency factors gain interests due to high demand from generation of induced pluripotent stem cells in regenerative medical therapy recently. This review will focus on demonstrate the recent advances in recombinant pluripotency factor production using various host.

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

scholarly journals Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation

2020 ◽  
Vol 21 (23) ◽  
pp. 9052
Author(s):  
Indrek Teino ◽  
Antti Matvere ◽  
Martin Pook ◽  
Inge Varik ◽  
Laura Pajusaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Target Genes ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Early Differentiation

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types.

Tyrosine kinase signalling in embryonic stem cells

2008 ◽  
Vol 115 (2) ◽  
pp. 43-55 ◽  
Author(s):  
Cecilia Annerén
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Self Renewal ◽  
Mouse Es Cells ◽  
Wide Range

Pluripotent ES (embryonic stem) cells can be expanded in culture and induced to differentiate into a wide range of cell types. Self-renewal of ES cells involves proliferation with concomitant suppression of differentiation. Some critical and conserved pathways regulating self-renewal in both human and mouse ES cells have been identified, but there is also evidence suggesting significant species differences. Cytoplasmic and receptor tyrosine kinases play important roles in proliferation, survival, self-renewal and differentiation in stem, progenitor and adult cells. The present review focuses on the role of tyrosine kinase signalling for maintenance of the undifferentiated state, proliferation, survival and early differentiation of ES cells.

Using embryonic stem cells to understand how glycosaminoglycans regulate differentiation

2014 ◽  
Vol 42 (3) ◽  
pp. 689-695 ◽  
Author(s):  
Rebecca J. Holley ◽  
Kate A. Meade ◽  
Catherine L.R. Merry
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cost Effective ◽  
Cell Types ◽  
Signalling Pathways ◽  
Stem Cell Maintenance ◽  
Morphogenetic Protein ◽  
High Concentrations

Differentiation and subsequent specialization of every cell within an organism is an intricate interwoven process. A complex network of signalling pathways eventually leads to the specification of a multitude of different cell types able to function co-operatively. HS (heparan sulfate) is a highly sulfated linear polysaccharide that resides at the pericellular cell–matrix interface where it dictates the binding and activity of a large number of proteins, including growth factors and morphogens such as members of the FGF (fibroblast growth factor) and BMP (bone morphogenetic protein) families. Embryonic stem cells derived from mice with mutations in components of the HS biosynthetic pathway provide an opportunity to dissect the contribution of HS to signalling pathways critical for regulating stem cell maintenance and differentiation. In addition to improving our understanding of signalling mechanisms, this knowledge enables the selection of exogenous HS saccharides to improve the efficiency and selectivity of directed differentiation protocols, offering a cost-effective alternative to high concentrations of expensive growth factors to drive differentiation towards a particular therapeutically relevant cell type.

scholarly journals Genome-wide identification and characterisation of HOT regions in the human genome

2016 ◽  
Author(s):  
Hao Li ◽  
Feng Liu ◽  
Chao Ren ◽  
Xiaochen Bo ◽  
Wenjie Shu
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Epigenetic Regulation ◽  
Human Cell ◽  
Embryonic Stem ◽  
Cell Types ◽  
Genome Wide ◽  
Development And Differentiation ◽  
Epigenetic Analysis

AbstractHOT (high-occupancy target) regions, which are bound by a surprisingly large number of transcription factors, are considered to be among the most intriguing findings of recent years. An improved understanding of the roles that HOT regions play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying HOT regions across the spectrum of human cell types. We characterised and validated HOT regions in embryonic stem cells (ESCs) and produced a catalogue of HOT regions in a broad range of human cell types. We found that HOT regions are associated with genes that control and define the developmental processes of the respective cell and tissue types. We also showed evidence of the developmental persistence of HOT regions at primitive enhancers and demonstrate unique signatures of HOT regions that distinguish them from typical enhancers and super-enhancers. Finally, we performed an epigenetic analysis to reveal the dynamic epigenetic regulation of HOT regions upon H1 differentiation. Taken together, our results provide a resource for the functional exploration of HOT regions and extend our understanding of the key roles of HOT regions in development and differentiation.

scholarly journals Isolation of human testicular cells and co-culture with embryonic stem cells

Reproduction ◽  
2018 ◽  
Vol 155 (2) ◽  
pp. 151-164 ◽  
Author(s):  
Meenakshi Gaur ◽  
Cyril Ramathal ◽  
Renee A Reijo Pera ◽  
Paul J Turek ◽  
Constance M John
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Lucifer Yellow ◽  
Colorimetric Detection ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Cell Types ◽  
Testicular Cells ◽  
Polarized Secretion ◽  
Cell Progression

Our overall goal is to create a three-dimensional human cell-based testicular model for toxicological and spermatogenesis studies. Methods to purify the major somatic testicular cells, namely Leydig cells (LCs), peritubular myoid cells (PCs) and Sertoli cells (SCs), from rats, mice and guinea pigs have been reported. In humans, the isolation of populations enriched for primary LCs, PCs or SCs also have described. One objective of this study was to determine if populations of cells enriched for all three of these cell types can be isolated from testes of single human donors, and we were successful in doing so from testes of three donors. Testes tissues were enzymatically digested, gravity sedimented and Percoll filtered to isolate populations enriched for LCs, PCs and SCs. LCs and PCs were identified by colorimetric detection of the expression of prototypical enzymes. Division of PCs and SCs in culture has been reported. We observed that primary human LCs could divide in culture by incorporation of 5-ethynyl-2′-deoxyuridine. SCs were identified and their functionality was demonstrated by the formation of tight junctions as shown by the expression of tight junction proteins, increased transepithelial electrical resistance, polarized secretion of biomolecules and inhibition of lucifer yellow penetration. Furthermore, we found that human SC feeder layers could facilitate germ cell progression of human embryonic stem cells (hESCs) by microarray analysis of gene expression.

scholarly journals Defining totipotency using criteria of increasing stringency

2020 ◽  
Author(s):  
Eszter Posfai ◽  
John Paul Schell ◽  
Adrian Janiszewski ◽  
Isidora Rovic ◽  
Alexander Murray ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Differentiated Cells ◽  
Totipotent Cell

AbstractTotipotency is the ability of a single cell to give rise to all the differentiated cells that build the conceptus, yet how to capture this property in vitro remains incompletely understood. Defining totipotency relies upon a variety of assays of variable stringency. Here we describe criteria to define totipotency. We illustrate how distinct criteria of increasing stringency can be used to judge totipotency by evaluating candidate totipotent cell types in the mouse, including early blastomeres and expanded or extended pluripotent stem cells. Our data challenge the notion that expanded or extended pluripotent states harbor increased totipotent potential relative to conventional embryonic stem cells under in vivo conditions.

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