Article
Multidisciplinary Sciences
Kalyan K. K. Sinha, Silvija Bilokapic, Yongming Du, Deepshikha Malik, Mario Halic
Summary: Pioneer transcription factors can access DNA in compacted chromatin, and the cooperation between OCT4 and SOX2 is important for pluripotency and reprogramming. However, the molecular mechanisms of how they function and cooperate on chromatin remain unclear.
Review
Biochemistry & Molecular Biology
Evgeny I. Bakhmet, Alexey N. Tomilin
Summary: POUV is a newly emerged class of POU transcription factors that play an important role in zygotic genome activation. In addition to their roles in neuroectoderm development similar to other POU-class proteins, they also have de novo functions, such as the pluripotency control by Oct4 in mammals.
Article
Biochemistry & Molecular Biology
Lucas Simoes Machado, Camila Martins Borges, Marina Amaro de Lima, Juliano Rodrigues Sangalli, Jacinthe Therrien, Lais Vicari de Figueiredo Pessoa, Paulo Fantinato Neto, Felipe Perecin, Lawrence Charles Smith, Flavio Vieira Meirelles, Fabiana Fernandes Bressan
Summary: Mechanisms of cell reprogramming by pluripotency-related transcription factors or nuclear transfer seem to be mediated by similar pathways. The study suggests that OCT4 and SOX2 may contribute to both processes and help elucidate the mechanisms responsible for pluripotency.
Article
Cell Biology
Md Mahfuz Al Mamun, Muhammad Riaz Khan, Yifu Zhu, Yuwei Zhang, Shuai Zhou, Ran Xu, Ihtisham Bukhari, Rick F. Thorne, Jinming Li, Xu Dong Zhang, Guangzhi Liu, Song Chen, Mian Wu, Xiaoyuan Song
Summary: This study identifies the E3 ubiquitin ligase Stub1 as a negative regulator of pluripotency in embryonic stem cells (ESCs). Stub1 catalyzes the degradation of Sox2, Oct4, and Nanog proteins, thereby reducing pluripotency. Deficiency of Stub1 enhances somatic cell reprogramming and delays differentiation, while its overexpression triggers ESC differentiation.
Article
Multidisciplinary Sciences
Nina Schmolka, Ino D. D. Karemaker, Richard Cardoso da Silva, Davide C. C. Recchia, Vincent Spegg, Jahnavi Bhaskaran, Michael Teske, Nathalie P. P. de Wagenaar, Matthias Altmeyer, Tuncay Baubec
Summary: The Nucleosome Remodeling and Deacetylation (NuRD) complex, consisting of MBD2 and MBD3 subunits, is crucial for cellular differentiation. In this study, the authors investigated the role of different MBD2 and MBD3 isoforms in rescuing the differentiation block observed in Mbd3 knockout mouse embryonic stem cells. They found that MBD3 is essential for neuronal differentiation, but its MBD domain is not required. Additionally, they identified that MBD2 isoforms can replace MBD3 during lineage commitment, with MBD2b fully rescuing the phenotype.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Jerry Hung-Hao Lo, Miguel Edwards, Justin Langerman, Rupa Sridharan, Kathrin Plath, Stephen T. Smale
Summary: By examining dynamic ranges of gene expression, the authors found that Oct4 and Sox2 binding is enriched near genes with large dynamic ranges of expression. Their results suggest that Oct4 and Sox2 directly establish both active and silent transcriptional states in pluripotent cells at a large number of genes subject to dynamic regulation.
GENES & DEVELOPMENT
(2022)
Review
Biochemistry & Molecular Biology
Evgeny I. Bakhmet, Alexey N. Tomilin
Summary: Oct4, a class V POU-domain protein encoded by the Pou5f1 gene, is believed to be crucial in early mammalian development. Recent studies have questioned its role in embryo development and genome activation, with findings suggesting that Oct4 may not be necessary for certain processes like somatic cell reprogramming. Structural features are thought to play a key role in supporting the function of Oct4 in these processes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biology
Le Xiong, Erik A. Tolen, Jinmi Choi, Sergiy Velychko, Livia Caizzi, Taras Velychko, Kenjiro Adachi, Caitlin M. MacCarthy, Michael Lidschreiber, Patrick Cramer, Hans R. Schoeler
Summary: The transcription factor Oct4 is essential for stem cell pluripotency, and this study investigates its functions by depleting and recovering it in embryonic stem cells. Oct4 depletion results in loss of binding to enhancers and decreased mRNA synthesis of target genes involved in maintaining pluripotency. Partial recovery of Oct4 expression increases chromatin accessibility but does not fully restore enhancer transcription. These findings suggest that Oct4 has concentration-dependent activities.
Article
Cell Biology
Chia- Ko, Jacek Biesiada, Hesbon A. Zablon, Xiang Zhang, Mario Medvedovic, Alvaro Puga
Summary: Key regulatory decisions during cleavage divisions in mammalian embryogenesis determine the fate of preimplantation embryonic cells. The aryl hydrocarbon receptor (AHR) plays a crucial role in blastomere differentiation in early-stage embryos, and disruption of AHR functions can impair blastocyst formation, affecting transcriptional heterogeneity and pluripotency.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thomas Brouwer, Chi Pham, Artur Kaczmarczyk, Willem-Jan De Voogd, Margherita Botto, Petra Vizjak, Felix Mueller-Planitz, John van Noort
Summary: Research suggests that the length and sequence of linker DNA play crucial roles in nucleosome stacking, where twist is more restrictive than bend. Theoretical and experimental results indicate that stacking interactions are most stable when the linker DNA length is a multiple of 10 bp.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Shasha Li, Hui Liu, Weidong Liu, Ning Shi, Ming Zhao, Siyi Wanggou, Weiren Luo, Lei Wang, Bin Zhu, Xiang Zuo, Wen Xie, Cong Zhao, Yao Zhou, Longlong Luo, Xiang Gao, Xingjun Jiang, Caiping Ren
Summary: This study identified the functional role of the long noncoding RNA (lncRNA) ESRG, which is highly expressed in human pluripotent stem cells (hPSCs). The transcription of ESRG is directly regulated by the key self-renewal factor OCT4, and ESRG binds to the replication-licensing factor MCM2 to maintain its steady-state level and nuclear location. This protects against DNA replication errors and suppresses the activation of the p53 pathway, ultimately maintaining the self-renewal and pluripotency of hPSCs. These findings provide critical insights into the mechanisms underlying self-renewal and pluripotency maintenance in hPSCs by lncRNAs.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yuki Toyama, Robert W. Harkness, Lewis E. Kay
Summary: HtrA2, a mitochondrial protease, is crucial for cellular proteostasis and associated with neurodegenerative disorders. Research shows that substrate binding to PDZ domains primes neighboring subunits for substrate binding, leading to significant structural rearrangements for the enzyme to transition into an active conformation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
L. E. Wadkin, S. Orozco-Fuentes, I Neganova, M. Lako, R. A. Barrio, A. W. Baggaley, N. G. Parker, A. Shukurov
Summary: Enhancing the regulation of human embryonic stem cell pluripotency and differentiation trajectories is vital for their clinical applications. Analyzing the temporal and spatial dynamics of the pluripotency transcription factor OCT4 in hESC colonies reveals insights into its self-regulation and fluctuations within cells. Understanding the similarities in OCT4 expression among neighboring cells can provide valuable information about the behavior of proliferating hESC colonies.
Article
Cell & Tissue Engineering
Danial Hashemi Karoii, Hossein Azizi
Summary: In this study, the expression of OCT4 during the differentiation of SSCs into neurons was investigated. The results showed that OCT4 was expressed in SSCs, ES-like cells, and EBs, but not in neuron cells. Furthermore, OCT4 was found to be closely linked to the differentiation process and exhibited biological functions such as stem cell maintenance and reprogramming. Overall, this study provides valuable insights into the differentiation of SSCs into neurons and offers potential implications for neurogenesis and neuronal repair.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Cell Biology
Yuli Hu, Yang V. Li
Summary: Environmental changes can induce stress-induced cellular reprogramming, as evidenced by the expression of pluripotent stem cell markers following brief strong acid treatment. This phenomenon resulted in faster cell growth and shorter doubling time, along with sensitivity to metal ion chelation. The findings suggest that somatic cells have the potential to express pluripotent markers under stressful conditions, providing new insights into cellular survival mechanisms.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Review
Chemistry, Inorganic & Nuclear
Manoj Saxena, Sergio A. Loza-Rosas, Kavita Gaur, Shweta Sharma, Sofia C. Perez Otero, Arthur D. Tinoco
COORDINATION CHEMISTRY REVIEWS
(2018)
Article
Multidisciplinary Sciences
Manoj Saxena, Yamixa Delgado, Rohit Kumar Sharma, Shweta Sharma, Solimar Liz Ponce De Leon Guzman, Arthur D. Tinoco, Kai Griebenow
Article
Biotechnology & Applied Microbiology
Kai Fu, Constantinos Chronis, Abdenour Soufi, Giancarlo Bonora, Miguel Edwards, Stephen T. Smale, Kenneth S. Zaret, Kathrin Plath, Matteo Pellegrini
Review
Oncology
Charles A. C. Williams, Abdenour Soufi, Steven M. Pollard
SEMINARS IN CANCER BIOLOGY
(2020)
Article
Biochemical Research Methods
Clara L. van Emmerik, Ivana Gachulincova, Vincenzo R. Lobbia, Mark A. Daniels, Hans A. Heus, Abdenour Soufi, Frank H. T. Nelissen, Hugo van Ingen
ANALYTICAL BIOCHEMISTRY
(2020)
Article
Hematology
Camille Malouf, Eric T. B. Antunes, Michael O'Dwyer, Helene Jakobczyk, Franziska Sahm, Sophie-Luise Landua, Richard A. Anderson, Abdenour Soufi, Christina Halsey, Katrin Ottersbach
Summary: t(4;11) MLL-AF4 acute leukemia is one of the most aggressive malignancies in infants and children, with limited understanding of the molecular mechanisms driving disease progression. This study identifies miR-130b and miR-128a as downstream targets of MLL-AF4, contributing to the transition from pre-leukemia to acute leukemia in murine models. The overexpression of these miRNAs recapitulates human disease phenotypes, providing potential targets for novel therapeutic approaches.
Article
Chemistry, Multidisciplinary
Angela C. Evans, Kelly A. Martin, Manoj Saxena, Sandra Bicher, Elizabeth Wheeler, Emilio J. Cordova, Christopher D. Porada, Graca Almeida-Porada, Takamitsu A. Kato, Paul F. Wilson, Matthew A. Coleman
Summary: The bioavailability of curcumin, a natural polyphenol with antioxidant and anti-inflammatory properties, is improved by incorporating it into biomimetic nanolipoprotein particles. This formulation enhances water solubility and loading capacity, making it a potential method for drug delivery in various applications.
Article
Cell Biology
Aida Costa, Lynn M. Powell, Mattias Malaguti, Abdenour Soufi, Sally Lowell, Andrew P. Jarman
Summary: The research discovered that the combined activities of Gfi1 and Pou4f3 repurpose Atoh1 from a neuronal to an inner ear hair cell determinant. Gfi1 plays a key role in this lineage switch, acting both as a repressor and a co-activator.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Rohit Kumar Sharma, Manoj Saxena, Crystal A. O'Neill, Hector A. R. Ramos, Kai Griebenow