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Stadtfeld, Matthias

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Stadtfeld

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Matthias

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Stadtfeld, Matthias

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2009 - 20102

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Author's Publications: search.filters.isAuthorOfPublication.16d9437c-5ae6-412a-ab63-4201030f9ce2

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    Cell Type of Origin Influences the Molecular and Functional Properties of Mouse Induced Pluripotent Stem Cells
    (Nature Publishing Group, 2010) Polo, Jose M.; Liu, Susanna; Figueroa, Maria Eugenia; Kulalert, Warakorn; Eminli, Sarah; Tan, Kah Yong; Apostolou, Effie; Stadtfeld, Matthias; Li, Yushan; Shioda, Toshihiro; Natesan, Sridaran; Wagers, Amy; Melnick, Ari; Evans, Todd; Hochedlinger, Konrad
    Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.
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    Fibroblast-Derived Induced Pluripotent Stem Cells Show No Common Retroviral Vector Insertions
    (Wiley Subscription Services, Inc., A Wiley Company, 2009) Varas, Florencio; de Andres-Aguayo, Luisa; di Tullio, Alessandro; Pantano, Lorena; Notredame, Cedric; Graf, Thomas; Stadtfeld, Matthias; Maherali, Nimet A; Hochedlinger, Konrad
    Several laboratories have reported the reprogramming of mouse and human fibroblasts into pluripotent cells, using retroviruses carrying the Oct4, Sox2, Klf4, and c-Myc transcription factor genes. In these experiments the frequency of reprogramming was lower than 0.1% of the infected cells, raising the possibility that additional events are required to induce reprogramming, such as activation of genes triggered by retroviral insertions. We have therefore determined by ligation-mediated polymerase chain reaction (LM-PCR) the retroviral insertion sites in six induced pluripotent stem (iPS) cell clones derived from mouse fibroblasts. Seventy-nine insertion sites were assigned to a single mouse genome location. Thirty-five of these mapped to gene transcription units, whereas 29 insertions landed within 10 kilobases of transcription start sites. No common insertion site was detected among the iPS clones studied. Moreover, bioinformatics analyses revealed no enrichment of a specific gene function, network, or pathway among genes targeted by retroviral insertions. We conclude that Oct4, Sox2, Klf4, and c-Myc are sufficient to promote fibroblast-to-iPS cell reprogramming and propose that the observed low reprogramming frequencies may have alternative explanations.