Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility DOI Creative Commons
Renhong Lu, Bowen Lin,

Zheyi Lin

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Cell fate determination and transition are of paramount importance in biology medicine. Naive pluripotency could be achieved by reprogramming differentiated cells. However, the mechanism is less clear. Osmolarity an essential physical factor that acts on living cells, especially for pluripotent but its significance cell remains unexplored. To investigate role osmolarity underlying mechanism. Flow cytometry, quantitative real-time PCR, teratoma chimeric mice assays were performed to assess efficiency characterize iPSCs. TEM, immunofluorescence staining, western blot, chemical treatment genetic modification utilized evaluate morphology, signaling pathways, cytoskeleton nuclear structure. Multiomic sequencings applied unveil transcriptome, histone markers chromatin accessibility EpiSCs hypo-osmotic condition. In condition, increased over 60-fold than iso-osmotic cells (1100 vs 18 colonies per 3 × 105 cells), whereas no colony formed hyper-osmotic As expected, converted displayed naive pluripotency. The exhibited larger size, area heterochromatin; ATAC-seq ChIP-seq confirmed gene loci with more H3K27ac. Mechanistically, hypo-osmolarity activated PI3K-AKT-SP1 EpiSCs, which reshaped nucleoskeleton, resulting genome reorganization expression. contrast, delayed ESCs' exit from Moreover, MEFs reprograming, promoted conversion Hypo-osmolarity promotes remodeling cytoskeleton, nucleoskeleton via pathway.

Language: Английский

Degradable and Multifunctional PEG-Based Hydrogels Formed by iEDDA Click Chemistry with Stable Click-Induced Supramolecular Interactions DOI Creative Commons

Nathan H. Dimmitt,

Chien‐Chi Lin

Macromolecules, Journal Year: 2024, Volume and Issue: 57(4), P. 1556 - 1568

Published: Feb. 16, 2024

The inverse electron demand Diels-Alder (iEDDA) reactions are highly efficient click chemistry increasingly utilized in bioconjugation, live cell labeling, and the synthesis modification of biomaterials. iEDDA have also been used to cross-link tetrazine (Tz) norbornene (NB) modified macromers [e.g., multiarm poly(ethylene glycol) or PEG]. In these hydrogels, Tz-NB adducts exhibit stable supramolecular interactions with a high hydrolytic stability. Toward engineering new class PEG-based hydrogels adaptable properties, we previously reported group NB-derivatized PEG via reacting hydroxyl-terminated carbic anhydride (CA). this work, show that cross-linked by PEGNB

Language: Английский

Citations

4
Soft Polyethylene Glycol Hydrogels Support Human PSC Pluripotency and Morphogenesis DOI Creative Commons

M. Seitz,

Yuanhui Song,

Xiaojun Lian

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(7), P. 4525 - 4540

Published: June 19, 2024

Lumenogenesis within the epiblast represents a critical step in early human development, priming embryo for future specification and patterning events. However, little is known about specific mechanisms that drive this process due to inability study vivo. While pluripotent stem cell (hPSC)-based models recapitulate many aspects of epiblast, most approaches generating these 3D structures rely on ill-defined, reconstituted basement membrane matrices. Here, we designed synthetic, nonadhesive polyethylene glycol (PEG) hydrogel matrices better understand role matrix mechanical cues iPSC morphogenesis, specifically elastic modulus. First, identified narrow range moduli were conducive hPSC viability, pluripotency, differentiation. We then used platform investigate effects modulus lumenogenesis, finding intermediate stiffness yielded epiblast-like aggregates. Conversely, stiffer impeded lumen formation apico-basal polarization, while softest polarized but aberrant structures. Our approach offers simple, modular modeling investigating its morphogenesis.

Language: Английский

Citations

3
The role of extracellular matrix viscoelasticity in development and disease DOI Creative Commons
Olivia Courbot,

Alberto Elósegui-Artola

npj Biological Physics and Mechanics., Journal Year: 2025, Volume and Issue: 2(1)

Published: April 3, 2025

Abstract For several decades, research has studied the influence of extracellular matrix (ECM) mechanical properties in cell response, primarily emphasising its elasticity as main determinant and tissue behaviour. However, ECM is not purely elastic; it viscoelastic. viscoelasticity now emerged a major regulator collective dynamics. This review highlights recent findings on role development pathology.

Language: Английский

Citations

0
The fusion of physics and biology in early mammalian embryogenesis DOI

Walter Piszker,

Mijo Simunovic

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2024, Volume and Issue: unknown, P. 31 - 64

Published: Jan. 1, 2024

Language: Английский

Citations

2
Long range mutual activation establishes Rho and Rac polarity during cell migration DOI Creative Commons
Henry De Belly, Andreu F. Gallen, Evelyn Strickland

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 2, 2024

In migrating cells, the GTPase Rac organizes a protrusive front, whereas Rho contractile back. How these GTPases are appropriately positioned at opposite poles of cell is unknown. Here we leverage optogenetics, manipulation mechanics, and mathematical modeling to reveal surprising long-range mutual activation front back polarity programs that complements their well-known local inhibition. This rooted in two distinct modes mechanochemical crosstalk. Local Rac-based protrusion stimulates side via membrane tension-based mTORC2. Conversely, Rho-based contraction induces cortical-flow-based remodeling membrane-to-cortex interactions leading PIP2 release, PIP3 generation, cell. We develop minimal unifying model explain how this mechanical facilitation biochemical inhibition enable robust global partitioning. Finally, validate importance context chemoattractant-based polarization migration primary human lymphocytes. Our findings demonstrate actin cortex plasma function as an integrated system for partitioning during likely other cellular contexts.

Language: Английский

Citations

1
Novel imaging and biophysical approaches to study tissue hydraulics in mammalian folliculogenesis DOI Creative Commons
Jake Turley,

Kim Whye Leong,

Chii Jou Chan

et al.

Biophysical Reviews, Journal Year: 2024, Volume and Issue: 16(5), P. 625 - 637

Published: Oct. 1, 2024

Abstract A key developmental stage in mammalian folliculogenesis is the formation of a fluid-filled lumen (antrum) prior to ovulation. While it has long been speculated that follicular fluid essential for oocyte maturation and ovulation, little known about morphogenesis mechanisms driving antrum potentially due challenges imaging tissue dynamics large tissues. Misregulation such processes leads anovulation, hallmark infertility ageing diseases as polycystic ovary syndrome (PCOS). In this review, we discuss recent advances deep techniques, machine learning theoretical approaches have applied study development diseases. We propose an integrative approach combining these techniques understanding physics hydraulics follicle ovarian functions.

Language: Английский

Citations

1
Actin pushes open a leaky lumen DOI
Jia Guo, Yue Shao

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 587 - 588

Published: May 1, 2024

Language: Английский

Citations

0
Temporal and anteriorly positioned mitotic zones drive asymmetric microtubule patterns needed for Left-Right Organizer development DOI Creative Commons

Yan Wu,

Yiling Lan,

Favour Ononiwu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Summary Cellular proliferation is vital for tissue development, including the Left-Right Organizer (LRO), a transient organ critical establishing vertebrate LR body plan. This study investigates cell redistribution and role of specific progenitor cells in LRO formation, focusing on lineage behavior. Using zebrafish as model, we mapped all mitotic events Kupffer’s Vesicle (KV), revealing an FGF-dependent, anteriorly enriched pattern. With KV-specific fluorescent microtubule (MT) line, observed that spindles align along KV’s longest axis until rosette stage, form after spin, are excluded from KV. Early aligned assemble cytokinetic bridges point MT bundles toward tight junction where will initially form. Post-abscission, repurposed remain targeted at center, facilitating actin recruitment. Additional cells, both non-cytokinetic, incorporated into rosette, repurposing or assembling before These findings show initial divisions crucial assembly, patterning, remodeling during KV development.

Language: Английский

Citations

0
Tissue engineered three-dimensional platforms for disease modeling and therapeutic development DOI
Erika E. Wheeler,

Kent Leach

Tissue Engineering Part B Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Three-dimensional (3D) tissue engineered models are under investigation to recapitulate architecture and functionality, thereby overcoming limitations of traditional 2D cultures preclinical animal models. This review highlights recent developments in 3D platforms designed model diseases vitro that affect numerous tissues organs, including cardiovascular, gastrointestinal, bone marrow, neural, reproductive, pulmonary systems. We discuss current technologies for models, highlighting the advantages, limitations, important considerations modeling diseases. Lastly, we future advancements necessary enhance reliability development disease.

Language: Английский

Citations

0
Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility DOI Creative Commons
Renhong Lu, Bowen Lin,

Zheyi Lin

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Cell fate determination and transition are of paramount importance in biology medicine. Naive pluripotency could be achieved by reprogramming differentiated cells. However, the mechanism is less clear. Osmolarity an essential physical factor that acts on living cells, especially for pluripotent but its significance cell remains unexplored. To investigate role osmolarity underlying mechanism. Flow cytometry, quantitative real-time PCR, teratoma chimeric mice assays were performed to assess efficiency characterize iPSCs. TEM, immunofluorescence staining, western blot, chemical treatment genetic modification utilized evaluate morphology, signaling pathways, cytoskeleton nuclear structure. Multiomic sequencings applied unveil transcriptome, histone markers chromatin accessibility EpiSCs hypo-osmotic condition. In condition, increased over 60-fold than iso-osmotic cells (1100 vs 18 colonies per 3 × 105 cells), whereas no colony formed hyper-osmotic As expected, converted displayed naive pluripotency. The exhibited larger size, area heterochromatin; ATAC-seq ChIP-seq confirmed gene loci with more H3K27ac. Mechanistically, hypo-osmolarity activated PI3K-AKT-SP1 EpiSCs, which reshaped nucleoskeleton, resulting genome reorganization expression. contrast, delayed ESCs' exit from Moreover, MEFs reprograming, promoted conversion Hypo-osmolarity promotes remodeling cytoskeleton, nucleoskeleton via pathway.

Language: Английский

Citations

0