scholarly journals Transcription Factors Active in the Anterior Blastema of Schmidtea mediterranea

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1782
Author(s):  
Yoko Suzuki-Horiuchi ◽  
Henning Schmitz ◽  
Carlotta Barlassina ◽  
David Eccles ◽  
Martina Sinn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Body Parts ◽  
Human Beings ◽  
Medical Treatments ◽  
Induced Pluripotent ◽  
Anterior Regeneration

Regeneration, the restoration of body parts after injury, is quite widespread in the animal kingdom. Species from virtually all Phyla possess regenerative abilities. Human beings, however, are poor regenerators. Yet, the progress of knowledge and technology in the fields of bioengineering, stem cells, and regenerative biology have fostered major advancements in regenerative medical treatments, which aim to regenerate tissues and organs and restore function. Human induced pluripotent stem cells can differentiate into any cell type of the body; however, the structural and cellular complexity of the human tissues, together with the inability of our adult body to control pluripotency, require a better mechanistic understanding. Planarians, with their capacity to regenerate lost body parts thanks to the presence of adult pluripotent stem cells could help providing such an understanding. In this paper, we used a top-down approach to shortlist blastema transcription factors (TFs) active during anterior regeneration. We found 44 TFs—31 of which are novel in planarian—that are expressed in the regenerating blastema. We analyzed the function of half of them and found that they play a role in the regeneration of anterior structures, like the anterior organizer, the positional instruction muscle cells, the brain, the photoreceptor, the intestine. Our findings revealed a glimpse of the complexity of the transcriptional network governing anterior regeneration in planarians, confirming that this animal model is the perfect playground to study in vivo how pluripotency copes with adulthood.

scholarly journals Development and Application of Endothelial Cells Derived From Pluripotent Stem Cells in Microphysiological Systems Models

2021 ◽  
Vol 8 ◽  
Author(s):  
Crystal C. Kennedy ◽  
Erin E. Brown ◽  
Nadia O. Abutaleb ◽  
George A. Truskey
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Organ Systems ◽  
Temporal Waveform ◽  
Induced Pluripotent

The vascular endothelium is present in all organs and blood vessels, facilitates the exchange of nutrients and waste throughout different organ systems in the body, and sets the tone for healthy vessel function. Mechanosensitive in nature, the endothelium responds to the magnitude and temporal waveform of shear stress in the vessels. Endothelial dysfunction can lead to atherosclerosis and other diseases. Modeling endothelial function and dysfunction in organ systems in vitro, such as the blood–brain barrier and tissue-engineered blood vessels, requires sourcing endothelial cells (ECs) for these biomedical engineering applications. It can be difficult to source primary, easily renewable ECs that possess the function or dysfunction in question. In contrast, human pluripotent stem cells (hPSCs) can be sourced from donors of interest and renewed almost indefinitely. In this review, we highlight how knowledge of vascular EC development in vivo is used to differentiate induced pluripotent stem cells (iPSC) into ECs. We then describe how iPSC-derived ECs are being used currently in in vitro models of organ function and disease and in vivo applications.

337 PROMOTER-DEPENDENT SILENCING OF REPROGRAMMING TRANSCRIPTION FACTORS IN MOUSE INDUCED PLURIPOTENT STEM CELLS PRODUCED WITH SLEEPING BEAUTY TRANSPOSON VECTORS

2015 ◽  
Vol 27 (1) ◽  
pp. 257
Author(s):  
S. G. Petkov ◽  
W. A. Kues ◽  
H. Niemann
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Sleeping Beauty ◽  
Rt Pcr ◽  
Induced Pluripotent ◽  
Pluripotency Genes

Epigenetic silencing of the transgenes has been considered a prerequisite for complete reprogramming of mouse somatic cells to induced pluripotent stem cells (miPSC). Here, we examined the activity status of the reprogramming transcription factors in miPSC produced with Sleeping Beauty (SB) transposon vectors carrying expression cassettes with the porcine OCT4, SOX2, c-MYC, and KLF4 (pOSMK) under the control of doxycycline (DOX)-inducible (TetO) or constitutive (CAG) promoters. Mouse embryo fibroblasts (MEF) were electroporated with SB-TetO-rTA-SV40pA-TetO-pOSMK-IRES-tdTomato-bGHpA (TetO group) or with SB-loxP-CAG-pOSMK-IRES-tdTomato-SV40pA-loxP (CAG group) together with SB100x (SB transposase). The cells were cultured on mitotically inactivated MEF feeders with DMEM supplemented with 20% knockout serum replacement, 2 mM l-glutamine, penicillin-streptomycin, nonessential amino acids, 0.1 mM 2-mercaptoethanol, 1000 U mL–1 of ESGRO, and 5 µg mL–1 of DOX. The miPSC colonies were individually picked, disaggregated to single cells, and propagated further under the same culture conditions. Three cell lines from each experimental group were examined for pluripotency characteristics, and the activity of the transgenes was monitored by the presence of tdTomato fluorescence and by RT-PCR. The miPSC produced with TetO vector silenced the transgene expression within 11 days post-transfection (in the presence of DOX) and upregulated the endogenous pluripotency genes Oct4, Sox2, Nanog, Rex1, and Utf1. These cells showed typical miPSC morphology and ability to differentiate into cells from the 3 primary germ layers in vitro and in vivo (teratomas). At the same time, the miPSC from the CAG group did not silence the transgenes even after 20 passages of continuous propagation, although they upregulated the endogenous pluripotency genes similarly to the TetO group. Moreover, these cells also showed ability to differentiate in vitro into cells from the 3 germ layers (contracting cardiac myocytes, neurons, epithelia) expressing differentiation markers Afp, Sox17, Gata4, Gata6, cardiac troponin, nestin, and PGP 9.5. Following Cre-mediated excision of the reprogramming cassette, the miPSC from the CAG group continued to self-renew and the expression of pluripotency markers Oct4, Sox2, Nanog, and Rex1 did not change significantly, as evidenced by real-time RT PCR (all P > 0.1), showing that these cells were not dependent on the transgenes for maintaining their pluripotency characteristics. Currently, we are investigating the ability of the miPSC from the CAG group to differentiate in vivo by producing teratomas and chimeras. The results from our preliminary investigations suggest that porcine transcription factors can be used for production of miPSC and that the silencing of the reprogramming transcription factors in miPSC is promoter-dependent, but may not be absolutely necessary for complete reprogramming to pluripotency.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

scholarly journals Biological importance of OCT transcription factors in reprogramming and development

2021 ◽  
Author(s):  
Kee-Pyo Kim ◽  
Dong Wook Han ◽  
Johnny Kim ◽  
Hans R. Schöler
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Donor Cell ◽  
Structural Components ◽  
Oct4 Expression ◽  
Reprogramming Factors ◽  
Induced Pluripotent

AbstractEctopic expression of Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Attempts to identify genes or chemicals that can functionally replace each of these four reprogramming factors have revealed that exogenous Oct4 is not necessary for reprogramming under certain conditions or in the presence of alternative factors that can regulate endogenous Oct4 expression. For example, polycistronic expression of Sox2, Klf4 and c-Myc can elicit reprogramming by activating endogenous Oct4 expression indirectly. Experiments in which the reprogramming competence of all other Oct family members tested and also in different species have led to the decisive conclusion that Oct proteins display different reprogramming competences and species-dependent reprogramming activity despite their profound sequence conservation. We discuss the roles of the structural components of Oct proteins in reprogramming and how donor cell epigenomes endow Oct proteins with different reprogramming competences.

Abstract 18663: Myocardial Heterogeneity in Heart With Postinfarction LV Remodeling and its Response to Cell Therapy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
weina cui ◽  
lei ye ◽  
albert jang ◽  
qiang xiong ◽  
pengyuan zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Treated Group ◽  
Border Zone ◽  
Flux Rate ◽  
Lv Remodeling ◽  
Myocardial Heterogeneity ◽  
Induced Pluripotent ◽  
Myocardial Bioenergetics

Rationale and Objective: Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury. Here, we investigated the functional impact and myocardial heterogeneity of bioenergetics using a porcine model of post infarction LV remodeling, and 2 dimensional chemical shift imaging (2D CSI) P-31 MR spectroscopy. Methods and Results: Ischemia-reperfusion (I/R) injury was surgically induced by occlusion distal LAD (OCCL) for 60 minutes in female Yorkshire farm swine (≈15kg), then randomly assigned to experimental groups: 1) 16 million human induced pluripotent stem cells (hiPSC) derived cardio myocytes (CMs), smooth muscle cells (SMC) and Endothelia cells (ECs) were directly myocardial injected through an epicardial fibrin patch (P+Cell, n= 4), 2) open patch (fibrin patch with no cell) were placed over the injury site (P w/o Cell, n=4). Size matched normal (n=9) and OCCL only (n=5) pigs were also studied. Four weeks after I/R, 2D CSI MRS studies were performed in a 9.4T/ 65 cm bore magnet. In vivo myocardial energetic mapping was achieved using 31 P 2D CSI. To measure the forward flux rate PCr to ATP, 2D CSI data were acquired with or without saturation on ATPγ resonance. I/R injury has a heterogeneous effect on LV myocardial bioenergetics. Myocardial creatine phosphate (PCr)/ATP ratio is significantly decreased in border zone (BZ) of the infarction than the myocardial areas remote from the scar (RZ) in cell treated and patch only groups (1.54+/- 0.05 vs 2.25 +/- 0.10, 1.49+/-0.07 vs 2.34 +/- 0.07, BZ vs RZ, p<0.05). The BZ PCr/ATP ratio is improved in the cell treated group compared with open patch group (1.71 +/- 0.05 vs. 1.54 +/- 0.05, p<0.05). The forward flux rate constant of PCr/ATP (k pcr→ATP ) in the border zone is slightly increased in cell treated group compared with patch only group (0.29 +/- 0.02 vs 0.22 +/- 0.04 , p<0.05) Conclusion: The approach of 2D CSI 31 P MRS can effectively map the heterogeneity of myocardial ATP flux rate via CK In Vivo porcine hearts. Postinfarction LV remodeling heart manifests pronounced heterogeneity in myocardial bioenergetics with most severe alterations in BZ. Cell therapy may effectively improve BZ myocardial bioenergetics.

scholarly journals Opportunities for Antibody Discovery Using Human Pluripotent Stem Cells: Conservation of Oncofetal Targets

2019 ◽  
Vol 20 (22) ◽  
pp. 5752 ◽  
Author(s):  
Heng Liang Tan ◽  
Andre Choo
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Oncofetal Antigens ◽  
Antibody Discovery ◽  
Induced Pluripotent ◽  
New Biomarkers

Pluripotent stem cells (PSCs) comprise both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The application of pluripotent stem cells is divided into four main areas, namely: (i) regenerative therapy, (ii) the study and understanding of developmental biology, (iii) drug screening and toxicology and (iv) disease modeling. In this review, we describe a new opportunity for PSCs, the discovery of new biomarkers and generating antibodies against these biomarkers. PSCs are good sources of immunogen for raising monoclonal antibodies (mAbs) because of the conservation of oncofetal antigens between PSCs and cancer cells. Hence mAbs generated using PSCs can potentially be applied in two different fields. First, these mAbs can be used in regenerative cell therapy to characterize the PSCs. In addition, the mAbs can be used to separate or eliminate contaminating or residual undifferentiated PSCs from the differentiated cell product. This step is critical as undifferentiated PSCs can form teratomas in vivo. The mAbs generated against PSCs can also be used in the field of oncology. Here, novel targets can be identified and the mAbs developed as targeted therapy to kill the cancer cells. Conversely, as new and novel oncofetal biomarkers are discovered on PSCs, cancer mAbs that are already approved by the FDA can be repurposed for regenerative medicine, thus expediting the route to the clinics.

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