https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/159777/1/j.cell.2006.07.024.pdf

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/49782/1/Yamanaka_Cell_131_5.pdf

Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.

Embryonic Stem Cell Lines Derived from Human Blastocysts

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

/pdf/human-adipose-tissue-is-a-source-of-multipotent-stem-cells-18jo72s52v.pdf

Human Adipose Tissue Is a Source of Multipotent Stem Cells

Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

/pdf/circular-rnas-are-a-large-class-of-animal-rnas-with-3ah6n8c4c0.pdf

Circular RNAs are a large class of animal RNAs with regulatory potency

Pluripotential cells are present in a mouse embryo until at least an early post-implantation stage, as shown by their ability to take part hi the formation of chimaeric animals1 and to form teratocarcinomas2. Until now it has not been possible to establish progressively growing cultures of these cells in vitro, and cell lines have only been obtained after teratocarcinoma formation in vivo. We report here the establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts. These cells are able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo. They have a normal karyotype.

Establishment in culture of pluripotential cells from mouse embryos

Introductory Remarks. Methodology. General Observations on the Staging of Postimplantation Mouse Embryos. General Observations on the Plates. Embryogenesis. Assessment of Developmental Stage of Pre- and Postimplantation Mouse Embryos Based on the Staging System of Theiler (1989): Preimplantation Period. Stages 1-5. Postimplantation Period. Stages 6-26. Scanning Electron Micrographs, and Special Systems: External Appearance of Intact Embryos Isolated between 7.5-9.5 Days p.c. (Text Associated with Plate 42). External Appearance of Intact Embryos Isolated between 9.5-11.5 Days p.c., and Differentiation of the Limbs over the Period from 9.5-117.5 Days p.c. (Text Associated with Plates 43-145). External Appearance of Intact Embryos Isolated between 11.5-118.5 Days p.c. (Text Associated with Plate 46). Differentiation of the Cephalic Region in Embryos Isolated between 9.5-111.5 Days p.c.--Scanning Electron Microscopy Series (Text Associated with Plate 47). Differentiation of the Eye--Scanning Electron Microscopy and Histological Series (Text Associated with Plates 48-153). Differentiation of the Pituitary (Text Associated with Plates 54-157). Development of the Tongue (Text Associated with Plate 58). Closure of the Palate (Text Associated with Plates 59-162). Morphology of the Spinal Cord (Text Associated with Plate 63). Early Stages in the Development of the Heart (Text Associated with Plates 64 and 65). Differentiation of the Lungs (Text Associated with Plate 66). Histochemical Demonstration of Primordial Germ Cells (Text Associated with Plate 67). Differentiation of the Urogenital Ridges, Gonads, and Genital Duct System (Text Associated with Plates 68-171). Differentiation of the Kidney (Text Associated with Plate 72). Discontinuities Occasionally Found in the Visceral Yolk Sac (Text Associated with Plates 73 and Plate 74, a-1f). Differentiation of the Placenta (Text Associated with Plate 74, g-1i and Plate 75). Disposition of the Extra-embryonic Membranes Associated with Various Types of Twinning (Text Associated with Plates 76-179). Asynchronous Implantation (Text Associated with Plate 80). Embryo Code Numbers for Serially-Sectioned Embryos Illustrated in Plates 1-141. Chapter References.

The Atlas of Mouse Development

The recent availability in culture of embryo-derived pluripotential cells which exhibit both a normal karyotype and a high differentiative ability has encouraged us to assess the potential of these cells to form functional germ cells following their incorporation into chimaeric mice We report here the results of blastocyst injection studies using three independently isolated XY embryo-derived cell lines (EK CP1 , EK CC1 1 and EKCC1 2) which produce a very high proportion (greater than 50%) of live-born animals that are overtly chimaeric Seven chimaeric male mice, derived from these three lines, have, so far, proved to be functional germ-line chimaeras

Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines

The neural membrane glycoprotein PrP (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. During pathogenesis, PrP accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. Although the involvement of PrP in the pathology of these diseases has long been known, the normal function of PrP remains unknown. Previous studies have shown that the PrP gene is expressed tissue specifically in adult animals, the highest levels in the brain, with intermediate levels in heart and lung and low levels in spleen. Prenatally, PrP mRNA has been detected in the brain of rat and hamster just prior to birth. In this study we have examined the expression of the PrP gene during mouse embryonic development by in situ hybridisation and observed dramatic regional and temporal gene expression in the embryo. Transcripts were detected in developing brain and spinal cord by 13.5 days. In addition, PrP gene expression was detected in the peripheral nervous system, in ganglia and nerve trunks of the sympathetic nervous system and neural cell populations of sensory organs. Expression of the PrP gene was not limited to neuronal cells, but was also detected in specific non-neuronal cell populations of the 13.5 and 16.5 day embryos and in extra-embryonic tissues from 6.5 days. This cell-specific expression suggests a pleiotropic role for PrP during development.

/pdf/the-prion-protein-gene-a-role-in-mouse-embryogenesis-17eodynkiu.pdf

The prion protein gene: a role in mouse embryogenesis?

Introduction. The Early Stages: From Fertilization to Implantation. The Postimplantation Embryo. Postimplantation Extra-Embryonic Development. Early Organogenesis. The Transitional Tissues: The Neural Crest. Somites And Their Derivatives (muscles, dermis, and vertebrae). The Branchial Arch System. The Major Organ Systems: The Heart and its Associated Vascular System. The Limbs. The Urogenital System. The Gut and its Associated Tissues. The Mouth and Nose Region. The Brain and Spinal Cord. The Eye and the Ear. The Skull. The Indexes: Introduction. Table of Mouse and Rat Developmental Stages. The Tissues Present in Each Stage of Mouse Development. Index of First Occurrences of Tissues. Glossary. References. Author Index. Tissue Index. Subject Index. The Wiring (Lineage) Diagrams

Matthew H. Kaufman

Papers

Establishment in culture of pluripotential cells from mouse embryos

The Atlas of Mouse Development

Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines

The prion protein gene: a role in mouse embryogenesis?

The anatomical basis of mouse development