Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are pluripotent stem cells derived from pre-implantation and post-implantation embryos, respectively. These cells are capable of interconversion through manipulation of key transcription factors and signaling pathways. While BAF chromatin remodeling complexes are known to play crucial roles in ESC self-renewal and pluripotency, their roles in EpiSCs and their interconversion with ESCs remain unclear. This study demonstrates that the LIF/STAT3 and Wnt signaling pathways, in conjunction with canonical BAF (cBAF) and PRC2 complexes, inhibit EpiSC gene expression, thereby preventing ESCs from converting to EpiSCs. Upon removal of LIF, the reduced LIF/STAT3 signaling lifts this inhibition, increasing TGF/Nodal pathway activity. Subsequently, the cBAF complex facilitates ESC to EpiSC conversion by promoting EpiSC gene expression. Furthermore, unlike cBAF, inhibition of the ncBAF complex downregulates TGF-β signaling, thereby hindering both ESC to EpiSC conversion and EpiSC maintenance. Moreover, this study revealed the dual mechanisms, methylating histone or non-histone protein STAT3, by which PRC2 components participate in the regulation of ESCs to EpiSCs. This research elucidates the interplay between distinct BAF complexes and specific signaling pathways in regulating the conversion and maintenance of ESCs and EpiSCs.
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http://dx.doi.org/10.1016/j.jbc.2024.108140 | DOI Listing |
Sci Rep
December 2024
Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Chronic complete spinal cord injury (SCI) is difficult to treat because of scar formation and cavitary lesions. While human iPS cell-derived neural stem/progenitor cell (hNS/PC) therapy shows promise, its efficacy is limited without the structural support needed to address cavitary lesions. Our study investigated a combined approach involving surgical scar resection, decellularized extracellular matrix (dECM) hydrogel as a scaffold, and hNS/PC transplantation.
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December 2024
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
The senescence of mesenchymal stem cells (MSCs) is closely related to aging and degenerative diseases. Curcumin exhibits antioxidant and anti-inflammatory effects and has been extensively used in anti-cancer and anti-aging applications. Studies have shown that curcumin can promote osteogenic differentiation, autophagy and proliferation of MSCs.
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December 2024
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Signaling interplay between the histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in mediating histaminergic itch has been well-established in mammalian models, but whether this is conserved in humans remains to be confirmed due to the difficulties in obtaining human sensory neurons (SNs) for experimentation. Additionally, previously reported species-specific differences in TRPV1 function indicate that use of human SNs is vital for drug candidate screening to have a higher chance of identifying clinically effective TRPV1 antagonists. In this study, we built a histamine-dependent itch model using peripheral SNs derived from human induced pluripotent stem cells (hiPSC-SNs), which provides an accessible source of human SNs for pre-clinical drug screening.
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December 2024
Department of Basic Sciences, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16066-840, Brazil.
Treatment of complex craniofacial deformities is still a challenge for medicine and dentistry because few approach therapies are available on the market that allow rehabilitation using 3D-printed medical devices. Thus, this study aims to create a scaffold with a morphology that simulates bone tissue, able to create a favorable environment for the development and differentiation of osteogenic cells. Moreover, its association with Plenum Guide, through cell-based tissue engineering (ASCs) for guided bone regeneration in critical rat calvarial defects.
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December 2024
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Lung cancer ranks as the most prevalent malignant neoplasm worldwide, contributing significantly to cancer-related mortality. Stemness is a well-recognized factor underlying radiotherapy resistance, recurrence and metastasis in non-small-cell lung cancer (NSCLC) patients. Our prior investigations have established the role of IQ motif containing GTPase-activating protein 3 (IQGAP3) in mediating radiotherapy resistance in lung cancer, but its impact on lung cancer stemness remains unexplored.
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