Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice

The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes. The induction is characterized by entry into the meiotic prophase, occurs synchronously and recapitulates cytological and transcriptome progression in vivo faithfully. Importantly, the female germ-cell induction necessitates a proper cellular competence—most typically, DNA demethylation of relevant genes—which is observed in appropriately propagated PGCs/PGCLCs, but not in PGCs/PGCLCs immediately after induction. This provides an explanation for the differential function of BMP signaling between PGC specification and female germ-cell induction. Our findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Development & Differentiation, Signal Transduction, Stem Cells Articles Source Type: research

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Gliomas account for approximately 80% of primary malignant tumors in the central nervous system. Despite aggressive therapy, the prognosis of patients remains extremely poor. Glioma stem cells (GSCs), considered a potential target of therapy for their crucial role in therapeutic resistance and tumor recurrence, are believed to be key factors in the disappointing outcome. Here, we took advantage of GSCs as the cell model to perform high-throughput drug screening, and the old antibiotic clofoctol was identified as the most effective compound, showing reduction of colony formation and induction of apoptosis of GSCs. Moreover,...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Contributors : Masahiro Hata ; Hiroto Kinoshita ; Yoku Hayakawa ; Mitsuru Konishi ; Mayo Tsuboi ; Yukiko Oya ; Hayato Nakagawa ; Hiroaki Fujiwara ; Samuel Asfaha ; Daniel L Worthley ; Yuki Muranishi ; Takahisa Furukawa ; Shunsuke Kon ; Hiroyuki Tomita ; Timothy C Wang ; Kazuhiko KoikeSeries Type : Expression profiling by arrayOrganism : Mus musculusMist1+ cells and parietal cells in mouse stomach were separatedly sorted, and RNAs were isolated.Mist1 (also known as Bhlha15) is expressed in gastric chief cells and gastric stem cells in mice. However, more specific genes for each population needs to be identified to better un...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusThis SuperSeries is composed of the SubSeries listed below.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
We report the application of chromatin immunoprecpitation (ChIP) and assay for transposase accessible chromatin (ATAC) followed by sequencing to assay chromatin response to metabolic perturbation.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Michael P Meers ; Derek H Janssens ; Steven HenikoffSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; OtherOrganism : Homo sapiensThough the in vitro structural and in vivo spatial characteristics of transcription factor (TF) binding are well defined, TF interactions with chromatin and other companion TFs during development are poorly understood. To analyze such interactions in vivo, we profiled several TFs across a time course of human embryonic stem cell differentiation via CUT&RUN epigenome profiling, and studied their interactions with nucleosomes and co-occurring TFs by En...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Other Homo sapiens Source Type: research
Contributors : Hirasaki Masataka ; Akihiko Okuda ; Norihiro KotaniSeries Type : Expression profiling by arrayOrganism : Mus musculusAs a first step for identifying hypothetical splenic stem cells for nonhematopoietic cells, densely-packed colony-forming cells were isolated from mouse spleen. Those which we designated as Splenic Adherent Colony-Forming Cells (SACCs) are positive for some of stem cell markers such as alkaline phosphatase and SSEA-1 antigen. We herewith determined global expression profiles of SACCs and control splenic adherent cells.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
ConclusionCurrent trends in data science suggest that the ideal model for decision support in head and neck cancers should be based on human-machine collaboration, namely on: (1) software-based algorithms, (2) physician innovation collaboratives, and (3) clinician mix optimization.
Source: Journal of the American College of Radiology - Category: Radiology Source Type: research
Source: Annals of Hematology - Category: Hematology Source Type: research
Source: Annals of Hematology - Category: Hematology Source Type: research
AbstractTo investigate the effect of chronic graft-versus-host disease (cGVHD) on the outcomes of acute myeloid leukemia (AML) patients who relapsed after allogenic hematopoietic cell transplantation, we performed a retrospective analysis on 218 patients with a median follow-up of 21.4 (3.4 –179.6) months. A total of 103 patients developed cGVHD, with a 2-year cumulative incidence of 48.9% (95% CI 42.1–55.7%). The estimated 3-year overall survival was 85.7% (95% CI 75.7–95.7%), 48.8% (95% CI 31.7–66.0%), and 54.1% (95% CI 44.3–63.8%) for patients with limited cGVHD, extensiv e cGVHD, and ...
Source: Annals of Hematology - Category: Hematology Source Type: research
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