Establishment of an induced pluripotent cell line (ABCRIi001-A) from an elderly female for ageing research.

Human induced pluripotent stem cells (hiPSCs) hold promises to model and understand human diseases, including those associated with ageing. Here, we describe ABCRIi001-A, a hiPSC line generated from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female enrolled in a study for development of an ageing score (ALFA Score). PBMCs were reprogrammed using three Sendai virus-based reprogramming vectors (hKOS, hc-Myc, and hKlf4).

Spatio-temporal dynamics of early somite segmentation in the chicken embryo.

During vertebrate embryo development, the body is progressively segmented along the anterior-posterior (A-P) axis early in development. The rate of somite formation is controlled by the somitogenesis embryo clock (EC), which was first described as gene expression oscillations of hairy1 (hes4) in the presomitic mesoderm of chick embryos with 15-20 somites. Here, the EC displays the same periodicity as somite formation, 90 min, whereas the posterior-most somites (44-52) only arise every 150 minutes, matched by a corresponding slower pace of the EC.

The vertebrate Embryo Clock: Common players dancing to a different beat.

Vertebrate embryo somitogenesis is the earliest morphological manifestation of the characteristic patterned structure of the adult axial skeleton. Pairs of somites flanking the neural tube are formed periodically during early development, and the molecular mechanisms in temporal control of this early patterning event have been thoroughly studied. The discovery of a molecular Embryo Clock (EC) underlying the periodicity of somite formation shed light on the importance of gene expression dynamics for pattern formation.

Cell-Fibronectin Interactions and Actomyosin Contractility Regulate the Segmentation Clock and Spatio-Temporal Somite Cleft Formation during Chick Embryo Somitogenesis.

Fibronectin is essential for somite formation in the vertebrate embryo. Fibronectin matrix assembly starts as cells emerge from the primitive streak and ingress in the unsegmented presomitic mesoderm (PSM). PSM cells undergo cyclic waves of segmentation clock gene expression, followed by Notch-dependent upregulation of in the rostral PSM which induces somite cleft formation.

gga-miRNOME, a microRNA-sequencing dataset from chick embryonic tissues.

MicroRNAs (miRNAs) are small non-coding RNA molecules, with sizes ranging from 18 to 25 nucleotides, which are key players in gene expression regulation. These molecules play an important role in fine-tuning early vertebrate embryo development. However, there are scarce publicly available miRNA datasets from non-mammal embryos, such as the chicken (Gallus gallus), which is a classical model system to study vertebrate embryogenesis.

Altered Cogs of the Clock: Insights into the Embryonic Etiology of Spondylocostal Dysostosis.

Spondylocostal dysostosis (SCDO) is a rare heritable congenital condition, characterized by multiple severe malformations of the vertebrae and ribs. Great advances were made in the last decades at the clinical level, by identifying the genetic mutations underlying the different forms of the disease. These were matched by extraordinary findings in the Developmental Biology field, which elucidated the cellular and molecular mechanisms involved in embryo body segmentation into the precursors of the axial skeleton.

NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning.

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of Germline depletion of Salsa and splice site mutations within first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken.

Brachyury Is Associated with Glioma Differentiation and Response to Temozolomide.

Glioblastomas (GBMs) are the most aggressive tumor type of the central nervous system, mainly due to their high invasiveness and innate resistance to radiotherapy and chemotherapy, with temozolomide (TMZ) being the current standard therapy. Recently, brachyury was described as a novel tumor suppressor gene in gliomas, and its loss was associated with increased gliomagenesis. Here, we aimed to explore the role of brachyury as a suppressor of glioma invasion, stem cell features, and resistance to TMZ.

The T-box transcription factor brachyury behaves as a tumor suppressor in gliomas.

The oncogene brachyury (TBXT) is a T-box transcription factor that is overexpressed in multiple solid tumors and is associated with tumor aggressiveness and poor patient prognosis. Gliomas comprise the most common and aggressive group of brain tumors, and at the present time the functional and clinical impact of brachyury expression has not been investigated previously in these neoplasms. Brachyury expression (mRNA and protein) was assessed in normal brain (n = 67), glioma tissues (n = 716) and cell lines (n = 42), and further in silico studies were undertaken using genomic databases totaling 3115 samples.

StemMapper: a curated gene expression database for stem cell lineage analysis.

Transcriptomic data have become a fundamental resource for stem cell (SC) biologists as well as for a wider research audience studying SC-related processes such as aging, embryonic development and prevalent diseases including cancer, diabetes and neurodegenerative diseases. Access and analysis of the growing amount of freely available transcriptomics datasets for SCs, however, are not trivial tasks. Here, we present StemMapper, a manually curated gene expression database and comprehensive resource for SC research, built on integrated data for different lineages of human and mouse SCs.

rdml: A Mathematica package for parsing and importing Real-Time qPCR data.

Objective: The purpose and objective of the research presented is to provide a package for easy importing of Real-Time PCR data markup language (RDML) data to Mathematica.

Results: Real-Time qPCR is the most widely used experimental method for the accurate quantification of gene expression. To enable the straightforward archiving and sharing of qPCR data and its associated experimental information, an XML-based data standard was developed-the Real-Time PCR data markup language (RDML)-devised by the RDML consortium.

Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer.

Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD).

Mechanisms of vertebrate embryo segmentation: Common themes in trunk and limb development.

Various ultradian rhythms ensure proper temporal regulations during embryo development. The embryo molecular clock, which was first identified in the presomitic mesoderm (PSM) underlying periodic somite formation, is one among them. Somites are the earliest manifestation of the segmented vertebrate body and they are formed with strict temporal precision.

The embryonic Brachyury transcription factor is a novel biomarker of GIST aggressiveness and poor survival.

Background: The T-box transcription factor Brachyury was recently reported to be upregulated and associated with prognosis in solid tumors. Here, we proposed to evaluate the potential use of Brachyury protein expression as a new prognostic biomarker in gastrointestinal stromal tumors (GIST).

Methods: Brachyury protein expression was analyzed by immunohistochemistry in a cohort of 63 bona fide GIST patients.

Getting a handle on embryo limb development: Molecular interactions driving limb outgrowth and patterning.

Development of the vertebrate embryo involves multiple segmentation processes to generate a functional, articulated organism. Cell proliferation, differentiation and patterning involve spatially and temporally regulated gene expression and signal transduction mechanisms. The developing vertebrate limb is an excellent model to study such fine-tuned regulations, whereby cells proliferate and are differentially sculptured along the proximal-distal, anterior-posterior and dorsal-ventral axes to form a functional limb.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo.

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown.

MicroRNA processing machinery in the developing chick embryo.

Gene expression regulation during embryo development is under strict regulation to ensure proper gene expression in both time and space. The involvement of microRNAs (miRNA) in early vertebrate development is documented and inactivation of different proteins involved in miRNA synthesis results in severe malformations or even arrests vertebrate embryo development. However, there is very limited information on when and in what tissues the genes encoding these proteins are expressed.

T-box transcription factor brachyury is associated with prostate cancer progression and aggressiveness.

Purpose: Successful therapy of patients with prostate cancer is highly dependent on reliable diagnostic and prognostic biomarkers. Brachyury is considered a negative prognostic factor in colon and lung cancer; however, there are no reports on Brachyury's expression in prostate cancer.

Experimental Design: In this study, we aimed to assess the impact of Brachyury expression in prostate tumorigenesis using a large series of human prostate samples comprising benign tissue, prostate intraepithelial neoplasia (PIN) lesions, localized tumor, and metastatic tissues.

Timing embryo segmentation: dynamics and regulatory mechanisms of the vertebrate segmentation clock.

All vertebrate species present a segmented body, easily observed in the vertebrate column and its associated components, which provides a high degree of motility to the adult body and efficient protection of the internal organs. The sequential formation of the segmented precursors of the vertebral column during embryonic development, the somites, is governed by an oscillating genetic network, the somitogenesis molecular clock. Herein, we provide an overview of the molecular clock operating during somite formation and its underlying molecular regulatory mechanisms.

Limb patterning: from signaling gradients to molecular oscillations.

The developing forelimb is patterned along the proximal-distal and anterior-posterior axes by opposing gradients of retinoic acid and fibroblast growth factors and by graded sonic hedgehog signaling, respectively. However, how coordinated patterning along both axes is accomplished with temporal precision remains unknown. The limb molecular oscillator hairy2 was recently shown to be a direct readout of the combined signaling activities of retinoic acid, fibroblast growth factor and sonic hedgehog in the limb mesenchyme.

Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb.

Embryo development requires precise orchestration of cell proliferation and differentiation in both time and space. A molecular clock operating through gene expression oscillations was first described in the presomitic mesoderm (PSM) underlying periodic somite formation. Cycles of HES gene expression have been further identified in other progenitor cells, including the chick distal limb mesenchyme, embryonic neural progenitors and both mesenchymal and embryonic stem cells.

Retinoic acid signaling regulates embryonic clock hairy2 gene expression in the developing chick limb.

Embryo development proceeds under strict temporal control and an embryonic molecular clock (EC), evidenced by cyclic gene expression, is operating during somite formation and limb development, providing temporal information to precursor cells. In somite precursor cells, EC gene expression and periodicity depends on Retinoic acid (RA) signaling and this morphogen is also essential for limb initiation, outgrowth and patterning. Since the limb EC gene hairy2 is differentially expressed along the proximal-distal axis as growth proceeds, concomitant with changes in flank-derived RA activity in the mesenchyme, we have interrogated the role of RA signaling on limb hairy2 expression regulation.

Comprehensive analysis of fibroblast growth factor receptor expression patterns during chick forelimb development.

Specific interactions between fibroblast growth factors (Fgf1-22) and their tyrosine kinase receptors (FgfR1-4) activate different signalling pathways that are responsible for the biological processes in which Fgf signalling is implicated during embryonic development. In the chick, several Fgf ligands (Fgf2, 4, 8, 9, 10, 12, 13 and 18) and the four FgfRs (FgfR 1, 2, 3 and 4) have been reported to be expressed in the developing limb. The precise spatial and temporal expression of these transcripts is important to guide the limb bud to develop into a wing/leg.

Sonic hedgehog in temporal control of somite formation.

Vertebrate embryo somite formation is temporally controlled by the cyclic expression of somitogenesis clock genes in the presomitic mesoderm (PSM). The somitogenesis clock is believed to be an intrinsic property of this tissue, operating independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh). This work revisits the notochord signaling contribution to temporal control of PSM segmentation by assessing the rate and number of somites formed and somitogenesis molecular clock gene expression oscillations upon notochord ablation.