Cell differentiation typically occurs with concomitant shape transitions to enable specialized functions. To adopt a different shape, cells need to change the mechanical properties of their surface. However, whether cell surface mechanics control the process of differentiation has been relatively unexplored. Here we show that membrane mechanics gate exit from naive pluripotency of mouse embryonic stem cells. By measuring membrane tension during early differentiation, we find that naive stem cells release their plasma membrane from the underlying actin cortex when transitioning to a primed state. By mechanically tethering the plasma membrane to the cortex by enhancing Ezrin activity or expressing a synthetic signaling-inert linker, we demonstrate that preventing this detachment forces stem cells to retain their naive pluripotent identity. We thus identify a decrease in membrane-to-cortex attachment as a new cell-intrinsic mechanism that is essential for stem cells to exit pluripotency.
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http://dx.doi.org/10.1016/j.stem.2020.10.017 | DOI Listing |
Sci Immunol
January 2025
Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Chronic low-grade inflammation observed in older adults, termed inflammaging, is a common feature underlying a multitude of aging-associated maladies including a decline in hematopoietic activity. However, whether suppression of inflammaging can preserve hematopoietic health span remains unclear, in part because of a lack of tools to measure inflammaging within hematopoietic stem cells (HSCs). Here, we identify thrombospondin-1 (Thbs1) as an essential regulator of inflammaging within HSCs.
View Article and Find Full Text PDFPLoS One
January 2025
Ionis Pharmaceuticals, Inc., Carlsbad, CA, United States of America.
Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created.
View Article and Find Full Text PDFPLoS One
January 2025
School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Skin and hair development is regulated by multitude of programs of activation and silencing of gene expression to maintain normal skin and hair follicle (HF) development, homeostasis, and cycling. Here, we have identified E74-like factor 5 (Elf5) transcription factor, as a novel regulator of keratinocyte proliferation and differentiation processes in skin. Expression analysis has revealed that Elf5 expression was localised and elevated in stem/progenitor cell populations of both the epidermis (basal and suprabasal) and in HF bulge and hair germ stem cell (SCs) compartments during skin and hair development and cycling.
View Article and Find Full Text PDFCell Rep
January 2025
Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200031, China. Electronic address:
Humans are widely exposed to phthalates, a common chemical plasticizer. Previous cohort studies have revealed that maternal exposure to monobutyl phthalate (MBP), a key metabolite of phthalates, is associated with neurodevelopmental defects. However, the molecular mechanism remains unclear.
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January 2025
The Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA. Electronic address:
The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrence. Here, we build a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass and the SVZ of 15 patients and two histologically normal SVZ samples as controls.
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