Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tunable Hydrogel Viscoelasticity Modulates Human Neural Maturation

ABSTRACT: Human induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in their ability to incorporate tunable biochemical and biomechanical signaling cues imparted by the neural extracellular matrix (ECM). The native brain ECM is viscoelastic and stress-relaxing, exhibiting a time-dependent response to an applied force. To recapitulate the remodelability of the neural ECM, we developed a family of protein-engineered hydrogels crosslinked with either static or dynamic covalent bonds that exhibit tunable stress relaxation rates. hiPSC-derived neural progenitor cells (NPCs) encapsulated within these gels underwent relaxation rate-dependent maturation. Specifically, NPCs within hydrogels with faster stress relaxation rates extended longer, more complex neuritic projections, exhibited decreased metabolic activity, and expressed higher levels of genes associated with neural maturation. By inhibiting actin polymerization, we observed decreased neuritic projections and a concomitant decrease in the expression of neural maturation genes. Taken together, these results suggest that microenvironmental viscoelasticity is sufficient to bias human NPC maturation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236334 | GEO | 2023/10/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Tryptophan zipper hydrogels: bioactive self-healing antimicrobial matrices

Project description:Natural materials can reversibly self-assemble into hierarchical networks with diverse structural and functional properties. Recreating these dynamic architectures using peptide-based synthetic materials has been an elusive goal, hindered by challenges in relating sequence to structure to function. Here we report on the de novo discovery of short peptides based on the “tryptophan zipper” (Trpzip) motif that self-assemble into hierarchically structured hydrogels. Trpzip hydrogels have a tunable modulus and show self-healing, stress relaxation, antimicrobial properties, and biocompatibility. The low yield point allows syringe extrusion with cytoprotection, and cell harvest with a flick of the wrist. Integrating a pendant cell adhesion motif promotes human intestinal organoid growth and differentiation, with polarity control and improved shape fidelity. Considering these unique characteristics, we anticipate Trpzip hydrogels will prove a versatile reagent for biotechnology and medicine.

2023-10-25 | PXD038870 | Pride

Tunable Hydrogel Viscoelasticity Modulates Human Neural Maturation

Project description:Tunable Hydrogel Viscoelasticity Modulates Human Neural Maturation

| PRJNA990647 | ENA

Enabling phenotypic drug discovery for neurological mitochondrial DNA disorders with patient-derived neural progenitor cells

Project description:Mitochondrial DNA (mtDNA) mutations predominantly cause neurological diseases. Searching for therapeutic strategies is hindered by the absence of viable neural model systems due to the challenges of engineering mtDNA. We demonstrate that neural progenitor cells (NPCs), rapidly obtained from human induced pluripotent stem cells (iPSCs), retain the parental mtDNA profile and exhibit mitochondrial maturation coupled with a metabolic switch away from glycolysis. Altered calcium homeostasis and mitochondrial hyperpolarization, both potential causes of neural impairment, were observed in iPSC-derived NPCs from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C). Phenotype-based high-content screenings (HCS) with FDA-approved compounds were carried out, leading to the identification of possible innovative counteracting agents. We propose iPSC-derived NPCs, displaying mild proliferative properties and proper genotype/metabotype, as a bona fide model system for the establishment of personalized phenotypic drug discovery for untreatable mtDNA disorders affecting the nervous system. Associated GEO accession number: GSE70071.

2017-03-31 | MSV000080849 | MassIVE

Enabling phenotypic drug discovery for neurological mitochondrial DNA disorders with patient-derived neural progenitor cells

2017-01-31 | PXD004977 | Pride

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoid

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to22 batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-01-31 | PXD023705 | Pride

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoids

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-02-10 | PXD023694 | Pride

Unveiling the development specific regenerative potential of spinal cord: insights from extracellular matrix

Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities than adult tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans compared to adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs), and facilitated axonal outgrowth and regeneration of spinal cord organoids than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in rats with spinal cord injury (SCI). It suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

2024-01-29 | PXD048991 |

Cell-specific crosstalk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone

Project description:Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially due to subventricular zone (SVZ) contact. Despite this, crosstalk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. Additionally, interaction with NPCs increases cathepsin B (CTSB) expression in GBM brain tumor initiating cells (BTICs). Lentiviral knockdown and recombinant protein experiments reveal both cell-intrinsic and soluble CTSB promote malignancy-associated BTIC phenotypes. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Finally, we show LV-proximal CTSB upregulation in patients, showing the relevance of this crosstalk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.

2024-06-24 | PXD044773 | Pride

Unveiling the Development Specific Regenerative Potential of Spinal Cord: Insights from Extracellular Matrix

Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities compared to adult tissues following injury. Although some cellular signaling pathways involved in the process have been identified, the specific role of extracellular matrix (ECM) responsible for neonatal spinal cord regeneration has remained elusive. Here we revealed that early developmental spinal cord contained a higher abundance of ECM proteins associated with neural development and axon growth but fewer inhibitory proteoglycans compared to adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserve the major difference of native spinal cord tissues in both stages. Compared to DASCM, DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs), as well as facilitated the long-distance axonal outgrowth and axon regeneration of spinal cord organoids. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to the remarkable neural regeneration ability. Furthermore, DNSCM demonstrated superior performance when used as a delivery vehicle for NPCs and organoids in rats with spinal cord injury (SCI). It suggests that ECM cues derived from different development stage might contribute to the distinct regeneration ability of spinal cord.

2023-09-13 | PXD045337 |

Increased neural progenitor proliferation in a hiPSC model of autism induces replication stress-associated genome instability [GRO-seq]

Project description:The association between macrocephaly and autism spectrum disorder (ASD) suggests that the mechanisms underlying excessive neural growth could contribute to ASD pathogenesis. Consistently, neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs) of ASD individuals with early developmental brain enlargement are inherently more proliferative than control NPCs. Here, we show that hiPSC-derived NPCs from ASD individuals with macrocephaly display an altered DNA replication program and increased DNA damage. When compared to the control NPCs, high throughput genome-wide translocation sequencing (HTGTS) demonstrates that ASD-derived NPCs harbored elevated DNA double-strand breaks in replication stress-susceptible genes, some of which are associated with ASD pathogenesis. Our results provide a mechanism linking hyperproliferation of NPCs with the pathogenesis of ASD by disrupting long neural genes involved in cell-cell adhesion and migration.

2020-01-30 | GSE140486 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data