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Author

Jim McWhir

Other affiliations: University of Edinburgh
Bio: Jim McWhir is an academic researcher from The Roslin Institute. The author has contributed to research in topics: Embryonic stem cell & Stem cell. The author has an hindex of 28, co-authored 55 publications receiving 11268 citations. Previous affiliations of Jim McWhir include University of Edinburgh.


Papers
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Journal ArticleDOI
27 Feb 1997-Nature
TL;DR: The birth of lambs from differentiated fetal and adult cells confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term and reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.
Abstract: Fertilization of mammalian eggs is followed by successive cell divisions and progressive differentiation, first into the early embryo and subsequently into all of the cell types that make up the adult animal. Transfer of a single nucleus at a specific stage of development, to an enucleated unfertilized egg, provided an opportunity to investigate whether cellular differentiation to that stage involved irreversible genetic modification. The first offspring to develop from a differentiated cell were born after nuclear transfer from an embryo-derived cell line that had been induced to become quiescent. Using the same procedure, we now report the birth of live lambs from three new cell populations established from adult mammary gland, fetus and embryo. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. The birth of lambs from differentiated fetal and adult cells also reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.

4,721 citations

Journal ArticleDOI
07 Mar 1996-Nature
TL;DR: This is the first report, to the authors' knowledge, of live mammalian offspring following nuclear transfer from an established cell line, and will provide the same powerful opportunities for analysis and modification of gene function in livestock species that are available in the mouse through the use of embryonic stem cells.
Abstract: Nuclear transfer has been used in mammals as both a valuable tool in embryological studies and as a method for the multiplication of 'elite' embryos. Offspring have only been reported when early embryos, or embryo-derived cells during primary culture, were used as nuclear donors. Here we provide the first report, to our knowledge, of live mammalian offspring following nuclear transfer from an established cell line. Lambs were born after cells derived from sheep embryos, which had been cultured for 6 to 13 passages, were induced to quiesce by serum starvation before transfer of their nuclei into enucleated oocytes. Induction of quiescence in the donor cells may modify the donor chromatin structure to help nuclear reprogramming and allow development. This approach will provide the same powerful opportunities for analysis and modification of gene function in livestock species that are available in the mouse through the use of embryonic stem cells.

1,874 citations

Journal ArticleDOI
01 Mar 1997-Nature
TL;DR: In this Letter in the 27 February issue, a production error led to the image for part b of Fig. 1 (fetal fibroblasts) being used twice, as parts b and c.
Abstract: Nature 385, 810-813(1997). In this Letter in the 27 February issue, a production error led to the image for part b of Fig. 1 (fetal fibroblasts) being used twice, as parts b and c. The correct image for Fig. Ic (mammary-derived cells) is shown below, and is also on the Nature web site and in reprints.

1,218 citations

Journal ArticleDOI
TL;DR: Dolly was the first sheep cloned and developed from the nuclei of fully differentiated adult cells, rather than from theuclei of early embryonic cells.
Abstract: Fertilization of mammalian eggs is followed by successive cell divisions and progressive differentiation, first into the early embryo and subsequently into all of the cell types that make up the adult animal. Transfer of a single nucleus at a specific stage of development, to an enucleated unfertilized egg, provided an opportunity to investigate whether cellular differentiation to that stage involved irreversible genetic modification. The first offspring to develop from a differentiated cell were born after nuclear transfer from an embryo-derived cell line that had been induced to become quiescent. Using the same procedure, we now report the birth of live lambs from three new cell populations established from adult mammary gland, fetus and embryo. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. The birth of lambs from differentiated fetal and adult cells also reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.

494 citations

Journal ArticleDOI
TL;DR: Elevated p53 levels were detected in liver, brain and kidney, supporting the hypothesised role for p53 as a monitor of DNA damage in mice with defective DNA repair.
Abstract: Defects in nucleotide excision repair are associated with the human condition xeroderma pigmentosum which predisposes to skin cancer. Mice with defective DNA repair were generated by targeting the excision repair cross complementing gene (ERCC-1) in the embryonic stem cell line, HM-1. Homozygous ERCC-1 mutants were runted at birth and died before weaning with liver failure. Examination of organs revealed polyploidy in perinatal liver, progressing to severe aneuploidy by 3 weeks of age. Elevated p53 levels were detected in liver, brain and kidney, supporting the hypothesised role for p53 as a monitor of DNA damage.

325 citations


Cited by
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Journal ArticleDOI
25 Aug 2006-Cell
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.

23,959 citations

Journal ArticleDOI
21 Dec 2007-Science
TL;DR: This article showed that OCT4, SOX2, NANOG, and LIN28 factors are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells.
Abstract: Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.

9,836 citations

Journal ArticleDOI
04 Jul 2002-Nature
TL;DR: It is reported here that cells co-purifying with mesenchymal stem cells—termed here multipotent adult progenitor cells or MAPCs—differentiate, at the single cell level, not only into meschymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro.
Abstract: We report here that cells co-purifying with mesenchymal stem cells--termed here multipotent adult progenitor cells or MAPCs--differentiate, at the single cell level, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. On transplantation into a non-irradiated host, MAPCs engraft and differentiate to the haematopoietic lineage, in addition to the epithelium of liver, lung and gut. Engraftment in the haematopoietic system as well as the gastrointestinal tract is increased when MAPCs are transplanted in a minimally irradiated host. As MAPCs proliferate extensively without obvious senescence or loss of differentiation potential, they may be an ideal cell source for therapy of inherited or degenerative diseases.

5,475 citations

Journal ArticleDOI
27 Feb 1997-Nature
TL;DR: The birth of lambs from differentiated fetal and adult cells confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term and reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.
Abstract: Fertilization of mammalian eggs is followed by successive cell divisions and progressive differentiation, first into the early embryo and subsequently into all of the cell types that make up the adult animal. Transfer of a single nucleus at a specific stage of development, to an enucleated unfertilized egg, provided an opportunity to investigate whether cellular differentiation to that stage involved irreversible genetic modification. The first offspring to develop from a differentiated cell were born after nuclear transfer from an embryo-derived cell line that had been induced to become quiescent. Using the same procedure, we now report the birth of live lambs from three new cell populations established from adult mammary gland, fetus and embryo. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. The birth of lambs from differentiated fetal and adult cells also reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.

4,721 citations

01 Jan 2000
TL;DR: This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices, in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation.
Abstract: NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

3,924 citations