UMD researcher discovers mechanisms and epigenetic markers with implications for diseases ranging from cancers to infertility

(University of Maryland) A UMD researcher uncovered new mechanisms that dictate the development of germline stem cells. Mechanisms were found to be associated with genes responsible for cancers and viral infections among other major diseases. Markers used to identify male germ cells were discovered, exploring how environmental factors or epigenetics affect these cells and providing significant insight into treatments for male infertility. Findings set the stage for chickens as a more prominent model organism for stem cell research.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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Publication date: Available online 10 October 2018Source: Trends in GeneticsAuthor(s): Aaron C. Goldstrohm, Traci M. Tanaka Hall, Katherine M. McKenneyMammalian Pumilio proteins, PUM1 and PUM2, are members of the PUF family of sequence-specific RNA-binding proteins. In this review, we explore their mechanisms, regulatory networks, biological functions, and relevance to diseases. Pumilio proteins bind an extensive network of mRNAs and repress protein expression by inhibiting translation and promoting mRNA decay. Opposingly, in certain contexts, they can activate protein expression. Pumilio proteins also regulate noncoding (...
Source: Trends in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract Mammalian Pumilio proteins, PUM1 and PUM2, are members of the PUF family of sequence-specific RNA-binding proteins. In this review, we explore their mechanisms, regulatory networks, biological functions, and relevance to diseases. Pumilio proteins bind an extensive network of mRNAs and repress protein expression by inhibiting translation and promoting mRNA decay. Opposingly, in certain contexts, they can activate protein expression. Pumilio proteins also regulate noncoding (nc)RNAs. The ncRNA, ncRNA activated by DNA damage (NORAD), can in turn modulate Pumilio activity. Genetic analysis provides new insig...
Source: Trends in Genetics : TIG - Category: Genetics & Stem Cells Authors: Tags: Trends Genet Source Type: research
Abstract Stem cells are ideal seeding cells, which have the potential for self-renewal and multiple differentiation, and they play a fundamental role in maintaining homeostasis and regenerating and repairing tissue. The discovery of female germline stem cells (FGSCs) brings much hope for the postnatal renewal of oocytes and solving some female infertility problems. Ovarian function declines with increasing female age. Moreover, ovarian germline stem cell niche-aging could be the main cause of ovarian senescence, which ultimately leads to decreased follicle generation, declining female fertility, and age-related di...
Source: Systems Biology in Reproductive Medicine - Category: Reproduction Medicine Authors: Tags: Syst Biol Reprod Med Source Type: research
Authors: Zarandi NP, Galdon G, Kogan S, Atala A, Sadri-Ardekani H Abstract While the survival rate of children with cancer is increasing, preserving fertility for prepubertal boys is still a challenge. Although intracytoplasmic sperm injection (ICSI) using frozen sperms has revolutionized infertility treatment, it is not applicable for the patients who undergo chemotherapy before puberty since spermatogenesis has not begun. Therefore, preserving spermatogonial stem cells (SSCs) as an experimental option can be provided to prepubertal patients at a risk of damage or loss of their SSCs due to cancer treatments and de...
Source: Stem Cells and Cloning: Advances and Applications - Category: Stem Cells Tags: Stem Cells Cloning Source Type: research
In this study, we reported a comprehensive genome-wide DNA methylation landscape in chicken germ cells, and transcriptomic dynamics was also presented. By uncovering DNA methylation patterns on individual genes, some genes accurately modulated by DNA methylation were found to be associated with cancers and virus infection, e.g., AKT1 and CTNNB1. Chicken-unique markers were also discovered for identifying male germ cells. Importantly, integrated epigenetic mechanisms were explored during male germ cell differentiation, which provides deep insight into the epigenetic processes associated with male germ cell differentiation a...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
A new study in the journal Nature Cell Biology has uncovered information about a key stage that human embryonic cells must pass through just before an embryo implants. The research, led by UCLA biologist Amander Clark, could help explain certain causes of infertility and spontaneous miscarriage.Infertility affects around 10 percent of the U.S. population, and roughly 15 to 20 percent of all pregnancies in the U.S. end in miscarriage. In many cases, the causes of infertility and miscarriage are unknown.A team led by Clark, a UCLA professor of molecular cell and developmental biology and member of the  Eli and Edythe Br...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Fanconi anemia (FA) is a relatively rare genetic condition with primary sequelae of bone marrow failure, hematologic malignancies, and squamous cell cancers (SCC) of head/neck, breast, and anogenital tract. Many patients require hematopoietic stem cell transplant (bone marrow transplant, BMT) to treat marrow dysfunction, but risk of future malignancies remains. Female patients are at risk of reproductive complications, including infertility related to primary ovarian insufficiency (POI) and gynecologic cancers.
Source: Journal of Pediatric and Adolescent Gynecology - Category: OBGYN Authors: Source Type: research
Abstract Forkhead box A2 (FOXA2) is a pioneer transcription factor involved in organ development, function and cancer. In the uterus, FOXA2 is essential for pregnancy and expressed specifically in the glands of the endometrium loss of FOXA2 function occurs during development of endometrial cancer in humans. The present study describes the development of a mouse model for conditional expression of mouse FOXA2. Using a system consisting of a minigene located at the Rosa26 locus, a CAG-S-mFOXA2 allele was generated in embryonic stem cells and subsequently in mice; before activation, the minigene is silent due to a fl...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research
UCLA researchers have made new inroads into understanding germ cell tumors, a diverse and rare group of cancers that begin in germ cells — the cells that develop into sperm and eggs. The researchers developed a protocol to recreate germ cell tumor cells from stem cells and used the new model to study the genetics of the cancer.Their findings could point the way toward new drugs to treat germ cell tumors, which account for around 3 percent of all cases of childhood and adolescent cancer.The study, published in Stem Cell Research, was led by Amander Clark, a UCLA professor of molecular cell and developmental biology an...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
This study was funded by the National Health and Medical Research Council, the Victorian Cancer Agency and a scholarship from the Chinese Scholarship Council. The authors have no conflicts of interest to declare.
Source: Molecular Human Reproduction - Category: Molecular Biology Source Type: research
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