scholarly journals Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

2021 ◽  
Vol 11 (12) ◽  
pp. 1314
Author(s):  
Caitlin E. Filby ◽  
Katherine A. Wyatt ◽  
Sally Mortlock ◽  
Fiona L. Cousins ◽  
Brett McKinnon ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Androgen Receptor Signaling ◽  
Disease States ◽  
Epithelial Marker ◽  
Embryonic Antigen ◽  
And Personalized Medicine ◽  
Menstrual Fluid ◽  
Stage Specific Embryonic Antigen

Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. We sought to overcome these limitations by generating organoids from (1) menstrual fluid (MF; MFO) using a method that enables the concurrent isolation of menstrual fluid supernatant, stromal cells, and leukocytes and (2) from biopsies and hysterectomy samples from women taking hormonal medication (EMO-H). MF was collected in a menstrual cup for 4–6 h on day 2 of menstruation. Biopsies and hysterectomies were obtained during laparoscopic surgery. Organoids were generated from all sample types, with MFO and EMO-H showing similar cell proliferation rates, proportion and localization of the endometrial basalis epithelial marker, Stage Specific Embryonic Antigen-1 (SSEA-1), and gene expression profiles. Organoids from different disease states showed the moderate clustering of epithelial secretory and androgen receptor signaling genes. Thus, MFO and EMO-H are novel organoids that share similar features to EMO but with the advantage of (1) MFO being obtained non-invasively and (2) EMO-H being obtained from 50% of the women who are not currently being studied through standard methods. Thus, MFO and EMO-H are likely to prove to be invaluable tools for gynecological research, enabling the population-wide assessment of endometrial health and personalized medicine.

scholarly journals Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Magali Kouidhi ◽  
Phi Villageois ◽  
Carine M. Mounier ◽  
Corinne Ménigot ◽  
Yves Rival ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Expression Profiles ◽  
Donor Site ◽  
Subcutaneous Fat ◽  
Gene Expression Profiles ◽  
Fat Grafting ◽  
Human Knee ◽  
Fat Depots ◽  
Adipose Derived Stromal Cells ◽  
Molecular Matching

Animal study findings have revealed that individual fat depots are not functionally equivalent and have different embryonic origins depending on the anatomic location. Mouse bone regeneration studies have also shown that it is essential to match theHoxcode of transplanted cells and host tissues to achieve correct repair. However, subcutaneous fat depots from any donor site are often used in autologous fat grafting. Our study was thus carried out to determine the embryonic origins of human facial (chin) and limb (knee) fat depots and whether they had similar features and molecular matching patterns. Paired chin and knee fat depots were harvested from 11 subjects and gene expression profiles were determined by DNA microarray analyses. Adipose-derived stromal cells (ASCs) from both sites were isolated and analyzed for their capacity to proliferate, form clones, and differentiate. Chin and knee fat depots expressed a differentHOXcode and could have different embryonic origins. ASCs displayed a different phenotype, with chin-ASCs having the potential to differentiate into brown-like adipocytes, whereas knee-ASCs differentiated into white adipocytes. These results highlighted different features for these two fat sites and indicated that donor site selection might be an important factor to be considered when applying adipose tissue in cell-based therapies.

scholarly journals Biophysical Techniques for Target Validation and Drug Discovery in Transcription-Targeted Therapy

2020 ◽  
Vol 21 (7) ◽  
pp. 2301 ◽  
Author(s):  
Mehdi Moustaqil ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Drug Discovery ◽  
Therapeutic Strategy ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Attractive Alternative ◽  
Specific Gene ◽  
Pharmaceutical Companies ◽  
Biochemical Activity ◽  
Biophysical Techniques ◽  
And Personalized Medicine

In the post-genome era, pathologies become associated with specific gene expression profiles and defined molecular lesions can be identified. The traditional therapeutic strategy is to block the identified aberrant biochemical activity. However, an attractive alternative could aim at antagonizing key transcriptional events underlying the pathogenesis, thereby blocking the consequences of a disorder, irrespective of the original biochemical nature. This approach, called transcription therapy, is now rendered possible by major advances in biophysical technologies. In the last two decades, techniques have evolved to become key components of drug discovery platforms, within pharmaceutical companies as well as academic laboratories. This review outlines the current biophysical strategies for transcription manipulation and provides examples of successful applications. It also provides insights into the future development of biophysical methods in drug discovery and personalized medicine.

scholarly journals Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease

2017 ◽  
Author(s):  
Guofeng Meng ◽  
Hongkang Mei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Synaptic Function ◽  
Core Network ◽  
Disease Etiology ◽  
Transcriptional Dysregulation ◽  
Disease States ◽  
Human And Mouse

AbstractBackgroundThe pathogenesis of Alzheimer’s disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes.MethodsApplying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states.Results97 genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimer’s disease. Both the co-expression and differential co-expression analysis suggested these genes to be interconnected as a core network and that their regulations were strengthened during the transition to disease states. Functional studies suggested the dysregulated genes to be associated with aging and synaptic function. Further, we checked the evolutionary conservation of the gene co-expression and found that human and mouse brain might have divergent transcriptional co-regulation even when they had conserved gene expression profiles.ConclusionOverall, our study reveals a profile of transcriptional dysregulation in the genesis of Alzheimer’s disease by forming a core network with altered regulation; the core network is associated with Alzheimer’s diseases by affecting the aging and synaptic functions related genes; the gene regulation in brain may not be conservative between human and mouse.

scholarly journals Predicting the Remaining Lifespan and Cultivation-Related Loss of Osteogenic Capacity of Bone Marrow Multipotential Stromal Cells Applicable across a Broad Donor Age Range

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Sarah M. Churchman ◽  
Sally A. Boxall ◽  
Dennis McGonagle ◽  
Elena A. Jones
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Cpg Islands ◽  
Gene Expression Profiles ◽  
Donor Age ◽  
Diverse Range ◽  
Healthy Donors ◽  
Population Doublings ◽  
Age Range

Background and Objectives. Culture expanded multipotential stromal cells (MSCs) have considerable potential for bone regeneration therapy but their wider use is constrained by the lack of simple and predictive assays of functional potency. Extended passaging leads to loss of multipotency but speed of decline depends on MSC donor age. The aim of this study was to develop an assay predictive of MSC culture longevity applicable to a broad donor age range. Materials and Methods. Bone marrow (BM, n=7) was obtained from a diverse range (2–72 years) of healthy donors. MSCs were culture expanded to senescence and their osteoprogenitor content, gene expression profiles, epigenetic signature, and telomere behaviour were measured throughout. Output data was combined for modelling purposes. Results. Regardless of donor age, cultures’ osteoprogenitor content correlated better with remaining lifespan (population doublings before senescence, PD-BS) than proliferative history (accrued PDs). Individual gene’s expression or telomere length did not predict PD-BS but methylation of individual CpG islands did, PRAMEF2 in particular (r=0.775). Coupling the steep relationship of relative SPARC expression with PD-BS (r=-0.753) the formula SPARC × 1/PREMEF2 gave an improved correlation (r=-0.893). Conclusion. A formula based on SPARC mRNA and PRAMEF2 methylation may be used to predict remaining BM-MSC longevity and related loss of multipotentiality independent of donor age.

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