A5036570118- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Nuclear Receptors and Signaling
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pancreatic function and diabetes
- RNA Research and Splicing
- MicroRNA in disease regulation
- Lysosomal Storage Disorders Research
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- Cancer-related molecular mechanisms research
Harvard University
2023-2025
Max Planck Institute for Molecular Biomedicine
2016-2024
Max Planck Society
2023
TU Dresden
2015
Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology understand the biology of myelin diseases develop treatments for such disorders. Here, we demonstrate that induction three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor is sufficient rapidly O4+ OL with an efficiency up 70% 28 d global gene-expression profile comparable primary OL. We further...
Oct4 is widely considered the most important among four Yamanaka reprogramming factors. Here, we show that combination of Sox2, Klf4, and cMyc (SKM) suffices for mouse somatic cells to induced pluripotent stem (iPSCs). Simultaneous induction Sox2 in fibroblasts triggers immediate retroviral silencing, which explains discrepancy with previous studies attempted but failed generate iPSCs without using vectors. SKM could partially activate pluripotency network, even Oct4-knockout fibroblasts....
Abstract Oct4, along with Sox2 and Klf4 (SK), can induce pluripotency but structurally similar factors like Oct6 cannot. To decode why Oct4 has this unique ability, we compare Oct4-binding, accessibility patterns transcriptional waves an mutant defective in the dimerization (Oct4 defSox2 ). We find that initial silencing of somatic program proceeds indistinguishably or without Oct4. mitigates mesenchymal-to-epithelial transition derails reprogramming. These effects are a consequence...
R-loops modulate genome stability and regulate gene expression, but the functions regulatory mechanisms of in stem cell biology are still unclear. Here, we profiled during somatic reprogramming found that dynamic changes essential for occurred before expression. Disrupting homeostasis by depleting RNaseH1 or catalytic inactivation at D209 (RNaseH1D209N) blocks reprogramming. Sox2, not any other factor Yamanaka cocktail, overcomes inhibitory effects activity loss on Sox2 interacts with...
Our understanding of pluripotency remains limited: iPSC generation has only been established for a few model species, pluripotent stem cell lines exhibit inconsistent developmental potential, and germline transmission demonstrated mice rats. By swapping structural elements between Sox2 Sox17, we built chimeric super-SOX factor, Sox2-17, that enhanced in five tested species: mouse, human, cynomolgus monkey, cow, pig. A swap alanine to valine at the interface Oct4 delivered gain function by...
The transcription factor Oct4 is essential for the maintenance and induction of stem cell pluripotency, but its functional roles are not fully understood. Here, we investigate functions by depleting subsequently recovering it in mouse embryonic cells (ESCs) conducting a time-resolved multiomics analysis. depletion leads to an immediate loss binding enhancers, accompanied decrease mRNA synthesis from target genes that part transcriptional network maintains pluripotency. Gradual enhancers does...
During the first lineage segregation, mammalian embryos generate inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to epiblast (EPI) that forms all types of body, an ability referred as pluripotency. The molecular mechanisms induce pluripotency in remain incompletely elucidated. Using knockout (KO) mouse models conjunction with low-input ATAC-seq RNA-seq, we found Oct4 Sox2 gradually come into play early ICM, coinciding initiation expression. activate pluripotency-related genes...
Abstract The generation of germline cells from human induced pluripotent stem (hiPSCs) represents a milestone toward in vitro gametogenesis. Methods to recapitulate development beyond primordial germ have relied on long-term cell culture, such as 3-dimensional organoid co-culture for ~four months. Using pipeline with highly parallelized screening, this study identifies combinations TFs that directly and rapidly convert hiPSCs oogonia-like (iOLCs). We demonstrate co-expression five – namely,...
During the first lineage segregation, mammalian embryos generate inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to epiblast (EPI) that forms all types of body, an ability referred as pluripotency. The molecular mechanisms induce pluripotency in remain incompletely elucidated. Using knockout (KO) mouse models conjunction with low-input ATAC-seq RNA-seq, we found Oct4 Sox2 gradually come into play early ICM, coinciding initiation expression. activate pluripotency-related genes...
Article22 December 2016Open Access Source Data Changing POU dimerization preferences converts Oct6 into a pluripotency inducer Stepan Jerabek orcid.org/0000-0002-3902-1939 Max Planck Institute for Molecular Biomedicine, Münster, Germany Search more papers by this author Calista KL Ng of Medical Biology, Singapore City, Guangming Wu Marcos J Arauzo-Bravo Biodonostia Health Research Institute, San Sebastián, Spain IKERBASQUE, Basque Foundation Science, Bilbao, Kee-Pyo Kim Daniel Esch Vikas...
Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method robustly convert fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation remyelination-promoting compounds and disease modeling. Ectopic expression SOX10, OLIG2, NKX6.2 results rapid generation O4+ cells, further differentiate MBP+ mature within 16 days. dc-hiOLs undergo chromatin remodeling express markers,...
The mechanisms underlying Parkinson's disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role cellular susceptibility to neurodegeneration. To study developmental contribution of GBA mutations PD we used patient-derived iPSCs carrying heterozygous N370S mutation gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction GCase...
OCT4 (also known as POU5F1) plays an essential role in reprogramming. It is the only member of POU (Pit-Oct-Unc) family transcription factors that can induce pluripotency despite sharing high structural similarities to all other members. Here, we discover OCT6 POU3F1) elicit reprogramming specifically human cells. OCT6-based does not alter mesenchymal-epithelial transition but attenuated through delayed activation network comparison with OCT4-based Creating a series reciprocal domain-swapped...
Highlights•Individually expressed BKSM generate iNSCs without a transient pluripotent state•Polycistronic expression produces Brn4-Klf4 fusion protein•The protein gains the ability to induce pluripotency•A shift in Brn4 binding from OctOct SoxOct motif enables induction of pluripotencySummarySimultaneous Oct4, Klf4, Sox2, and cMyc induces pluripotency somatic cells (iPSCs). Replacing Oct4 with neuro-specific factor leads transdifferentiation fibroblasts into induced neural stem (iNSCs)....
Abstract Since the revolutionary discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka, comparison between iPSCs and embryonic (ESCs) has revealed significant differences in their epigenetic states developmental potential. A recent compelling study published Nature Buckberry et al. 1 demonstrated that a transient-naive-treatment (TNT) could facilitate reprogramming improve potential human (hiPSCs). However, characterized bulk hiPSCs instead isolating clonal lines overlooked...
Chronic granulomatous disease (CGD) is an inherited immunodeficiency, caused by the inability of neutrophils to produce functional NADPH oxidase required for fighting microbial infections. The X-linked form CGD (X-CGD), which due mutations in CYBB (gp91phox) gene, a component oxidase, accounts about two-thirds cases. We derived induced pluripotent stem cells (iPSCs) from X-CGD patient keratinocytes using Flp recombinase excisable lentiviral reprogramming vector. For restoring gp91phox...
Transcription factor-driven cell fate engineering in pluripotency induction, transdifferentiation, and forward reprogramming requires efficiency, speed, maturity for widespread adoption clinical translation. Here, we used Oct4, Sox2, Klf4, c-Myc driven to evaluate methods enhancing tailoring transitions, through directed evolution with iterative screening of pooled mutant libraries phenotypic selection. We identified an artificially evolved enhanced POU factor (ePOU) that substantially...
During the first lineage segregation, mammalian embryos generate inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to epiblast (EPI) that forms all types of body, an ability referred as pluripotency. The molecular mechanisms induce pluripotency in remain incompletely elucidated. Using knockout (KO) mouse models conjunction with low-input ATAC-seq RNA-seq, we found Oct4 Sox2 gradually come into play early ICM, coinciding initiation expression. activate pluripotency-related genes...
Abstract Adenoviral early region 1A (E1A) is a viral gene that can promote cellular proliferation and de-differentiation in mammalian cells, features required for the reprogramming of somatic cells to pluripotent state. E1A has been shown interact with OCT4 as consequence, increase transcriptional activity. Indeed, are sufficient revert neuroepithelial hybrids pluripotency, demonstrated previous cell fusion experiments. However, role might play generation induced stem (iPSCs) not...
Abstract The vertebrate transcription factor SOX2 (SRY Homology Box 2) is essential for stem cell maintenance, a prominent (co)inductor of pluripotency in reprogramming technology, and an oncogenic driver transformation, therapy resistance, disease relapse cancer. These fate discriminatory events are currently understood as SOX2-imposed changes DNA activity the resultant co-transcriptional rewiring inside cell’s nucleus. Cytoplasmic forms SOX2, on other hand, receive comparatively little...
During the first lineage segregation, mammalian embryos generate inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to epiblast (EPI) that forms all types of body, an ability referred as pluripotency. The molecular mechanisms induce pluripotency in remain incompletely elucidated. Using knockout (KO) mouse models conjunction with low-input ATAC-seq RNA-seq, we found Oct4 Sox2 gradually come into play early ICM, coinciding initiation expression. directly activate pluripotency-related...