The Wnt/β-catenin pathway and Nanog are key regulators of embryonic stem cell (ESC) pluripotency and the reprogramming of somatic cells. Here, we demonstrate that the repression of Dkk1 by Nanog, which leads indirectly to β-catenin activation, is essential for reprogramming after fusion of ESCs overexpressing Nanog. In addition, β-catenin is necessary in Nanog-dependent conversion of preinduced pluripotent stem cells (pre-iPSCs) into iPSCs. The activation of β-catenin by Nanog causes fluctuations of β-catenin in ESCs cultured in serum plus leukemia inhibitory factor (serum+LIF) medium, in which protein levels of key pluripotency factors are heterogeneous. In 2i+LIF medium, which favors propagation of ESCs in a ground state of pluripotency with many pluripotency genes losing mosaic expression, we show Nanog-independent β-catenin fluctuations. Overall, we demonstrate Nanog and β-catenin cooperation in establishing naive pluripotency during the reprogramming process and their correlated heterogeneity in ESCs primed toward differentiation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2014.08.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-Risk MCL: Recognition and Treatment.
Blood
December 2024
The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States.
Significant progress in determining the molecular origins and resistance mechanisms of mantle cell lymphoma (MCL) has improved our understanding of the disease's clinical diversity. These factors greatly impact prognosis in MCL patients. Given the dynamic alterations in MCL clones and disease evolution, it is crucial to recognize high-risk prognostic factors at diagnosis and relapse.
View Article and Find Full Text PDFFate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs.
Cell Rep
January 2025
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
Neurogenic microRNAs 9/9 and 124 (miR-9/9-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9-124 fate erasure logic extends to the neuronal conversion of other somatic cell types remains unknown. Here, we uncover that miR-9/9-124 induces neuronal conversion of multiple cell types: dura fibroblasts, astrocytes, smooth muscle cells, and pericytes.
View Article and Find Full Text PDFA rapid chemical reprogramming system to generate human pluripotent stem cells.
Nat Chem Biol
January 2025
MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences and MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Chemical reprogramming enables the generation of human pluripotent stem (hCiPS) cells from somatic cells using small molecules, providing a promising strategy for regenerative medicine. However, the current method is time consuming, and some cell lines from different donors are resistant to chemical induction, limiting the utility of this approach. Here, we developed a fast reprogramming system capable of generating hCiPS cells in as few as 10 days.
View Article and Find Full Text PDFReconstitution of pluripotency from mouse fibroblast through Sall4 overexpression.
Nat Commun
December 2024
Center for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation.
View Article and Find Full Text PDFTranscription factor-mediated reprogramming to antigen-presenting cells.
Curr Opin Genet Dev
December 2024
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden; CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal. Electronic address:
Antigen-presenting cells (APCs) are a heterogenous group of immune cells composed by dendritic cells (DCs) and macrophages (Mϕ), which are critical for orchestrating immunity against cancer or infections. Several strategies have been explored to generate APC subsets, including enrichment from peripheral blood and differentiation from pluripotent or multipotent cells. During development, the generation of APC subsets is instructed by transcription factors (TFs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!