Data Entry Maintenance

Metadata Commons Identifier

HMC000112

Project Title

Fibrin Hydrogels Induce Mixed Dorsal/Ventral Spinal Neuron Identities During Differentiation of Human Induced Pluripotent Stem Cells

Project Description

<p>We hypothesized that generating spinal motor neurons (sMNs) from human induced pluripotent stem cell (hiPSC)-derived neural aggregates (NAs) using a chemically-defined differentiation protocol would be more effective inside of 3D fibrin hydrogels compared to 2D poly-L-ornithine(PLO)/laminin-coated tissue culture plastic surfaces. We performed targeted RNA-Seq using next generation sequencing to determine the substrate-specific differences in gene expression that regulate cell phenotype. Cells cultured on both substrates expressed sMN genes CHAT and MNX1, though persistent WNT signaling contributed to a higher expression of genes associated with interneurons in NAs cultured in 3D fibrin scaffolds. Cells in fibrin also expressed lower levels of astrocyte progenitor genes and higher levels of the neuronal-specific gene TUBB3, suggesting a purer population of neurons compared to 2D cultures. <br>STATEMENT OF SIGNIFICANCE: Fibrin scaffolds can support the neuronal differentiation of pluripotent stem cells. This study provides insight into how fibrin hydrogels affect neuronal induction by analyzing of the signaling pathways activated during the differentiation process. These insights can then be used to tailor the properties of these hydrogels to optimize the generation of sMNs for regenerative medicine applications.</p>

Project Funder(s)

Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation, Natural Sciences and Engineering Research Council of Canada (NSERC)

Project Institution(s)

University of Victoria

Project Investigator(s)

Meghan Robinson, John Edgar, Stephanie Willerth

Data Access Request URL*

Keywords

Fibrin, Gene expression, Laminin, Motor neuron, Neural progenitor, RNA-Seq, Stem cells

Publication Link

https://pubmed.ncbi.nlm.nih.gov/28088670

Study Completed

Post to REACH BC Platform

Cohort Name

Human induced pluripotent stem cell (hiPSC)-derived neural aggregates (NAs)

Cohort Size

Disease/Condition Studied

neurological disorders

Enrollment Time Window

Biobanking Consent Available

Medical History Available

Ethnicity Availability

Time Course

Patient Phenotypes

Patient Outcomes

Clinical Data Types Available

Time Course Data Points

Enrollment City

Groups

Project

Cohort

Enrollment City

Groups

Samples and Omics