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Jennifer L. Frane

Bio: Jennifer L. Frane is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Stem cell & Embryoid body. The author has an hindex of 4, co-authored 4 publications receiving 14432 citations.

Papers
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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

01 Jan 2007
TL;DR: Yu et al. as discussed by the authors proposed online material for induced pluripotent stem cell lines derived from human Somatic Cells, which can be used for transplanting human stem cells to humans.
Abstract: Supporting Online Material for Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells Junying Yu,* Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L. Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, James A. Thomson* *To whom correspondence should be addressed. E-mail: jyu@primate.wisc.edu (J.Y.); thomson@primate.wisc.edu (J.A.T.)

3,632 citations

Journal ArticleDOI
TL;DR: Feeder-independent human ES cell culture that includes protein components solely derived from recombinant sources or purified from human material is reported.
Abstract: We have previously reported that high concentrations of basic fibroblast growth factor (bFGF) support feeder-independent growth of human embryonic stem (ES) cells, but those conditions included poorly defined serum and matrix components. Here we report feeder-independent human ES cell culture that includes protein components solely derived from recombinant sources or purified from human material. We describe the derivation of two new human ES cell lines in these defined culture conditions.

1,246 citations

Journal ArticleDOI
TL;DR: Somatic cell nuclear transfer as discussed by the authors permits transacting factors resident in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state, which is called epigenetic activation.
Abstract: Because the mammalian embryo is regulated by epigenetic rather than genetic events, differentiation is—in principle—reversible. Somatic cell nuclear transfer permits trans-acting factors resident in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. The inves

289 citations

TL;DR: Four genes used to reprogram human somatic cells to pluripotent stem cells, which are cells that have the ability to develop into any specialized cell type making up the body, were identified.
Abstract: By: Wu, Ke On 2 December 2007, Science published a report on creating human induced pluripotent stem (iPS) cells from human somatic cells: “Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells.” This report came from a team of Madison, Wisconsin scientists: Junying Yu [5] , Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L. Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, and James A. Thomson [6] . Earlier that year Shinya Yamanaka [7] at Kyoto University [8] , Japan published a similar paper, “Generation of Germline-Competent Induced Pluripotent Stem Cells,” in Nature . Both papers independently identified four genes [9] used to reprogram human somatic cells to pluripotent stem cells [10] , which are cells that have the ability to develop into any specialized cell type making up the body. The reprogrammed somatic cells were referred to as iPS cells and they exhibit fundamental qualities of human embryonic stem (ES) cells. The idea of reversing the biological process whereby ES cells differentiate into somatic (adult) cells comes from the concept that development derives from epigenetic rather than genetic events. Based on this principle, differentiation [11] is reversible. In cloning [12] the sheep [13] Dolly, scientists were able to demonstrate that nuclei taken from differentiated adult mammalian cells have the ability to be reprogrammed into an undifferentiated state using the technique known as somatic cell nuclear transfer [14] (SCNT). In SCNT, an isolated nucleus [15] from a differentiated adult cell is fused with an enucleated egg [16] , an egg [16] with the nucleus [15] removed. The fused nuclei are reprogrammed creating human induced pluripotent stem (iPS) cells from human somatic cells: Pluripotent Stem Cell Lines Derived from Human Cells." published a similar paper,"Generation of Germline-Competent Induced Pluripotent Stem Cells," in Nature. Both papers independently identified four genes used to reprogram human somatic cells to pluripotent stem cells, which are cells that have the ability to develop into any specialized cell type making up the body. The reprogrammed somatic cells were referred to as iPS cells and they exhibit fundamental qualities of human embryonic stem (ES) cells.

Cited by
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01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
19 Nov 2009-Nature
TL;DR: The first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors were presented in this article.
Abstract: DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.

4,266 citations

Journal ArticleDOI
TL;DR: Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.
Abstract: Current neural induction protocols for human embryonic stem (hES) cells rely on embryoid body formation, stromal feeder co-culture or selective survival conditions. Each strategy has considerable drawbacks, such as poorly defined culture conditions, protracted differentiation and low yield. Here we report that the synergistic action of two inhibitors of SMAD signaling, Noggin and SB431542, is sufficient to induce rapid and complete neural conversion of >80% of hES cells under adherent culture conditions. Temporal fate analysis reveals the appearance of a transient FGF5(+) epiblast-like stage followed by PAX6(+) neural cells competent to form rosettes. Initial cell density determines the ratio of central nervous system and neural crest progeny. Directed differentiation of human induced pluripotent stem (hiPS) cells into midbrain dopamine and spinal motoneurons confirms the robustness and general applicability of the induction protocol. Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.

3,152 citations

Journal ArticleDOI
10 Jan 2008-Nature
TL;DR: The data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.
Abstract: Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.

3,035 citations