CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes.
2022; 13 (1): 5583
Myelin is required for rapid nerve signaling and is emerging as a key driver of CNS plasticity and disease. How myelin is built and remodeled remains a fundamental question of neurobiology. Central to myelination is the ability of oligodendrocytes to add vast amounts of new cell membrane, expanding their surface areas by many thousand-fold. However, how oligodendrocytes add new membrane to build or remodel myelin is not fully understood. Here, we show that CNS myelin membrane addition requires exocytosis mediated by the vesicular SNARE proteins VAMP2/3. Genetic inactivation of VAMP2/3 in myelinating oligodendrocytes caused severe hypomyelination and premature death without overt loss of oligodendrocytes. Through live imaging, we discovered that VAMP2/3-mediated exocytosis drives membrane expansion within myelin sheaths to initiate wrapping and power sheath elongation. In conjunction with membrane expansion, mass spectrometry of oligodendrocyte surface proteins revealed that VAMP2/3 incorporates axon-myelin adhesion proteins that are collectively required to form nodes of Ranvier. Together, our results demonstrate that VAMP2/3-mediated membrane expansion in oligodendrocytes is indispensable for myelin formation, uncovering a cellular pathway that could sculpt myelination patterns in response to activity-dependent signals or be therapeutically targeted to promote regeneration in disease.
View details for DOI 10.1038/s41467-022-33200-4
View details for PubMedID 36151203
Modeling myelin: A toolkit for exploring myelin's mysteries in vitro.
2021; 56 (9): 1215–17
In the myelin field, there is a lack of reliable in vitro tools to study myelination, especially using human cells. In this issue of Developmental Cell, James et al. present a guide to generating human iPSC-derived "myelinoids"-3D models of myelination that reliably achieve mature myelin formation.
View details for DOI 10.1016/j.devcel.2021.04.015
View details for PubMedID 33945781
Soft extracellular matrix enhances inflammatory activation of mesenchymal stromal cells to induce monocyte production and trafficking
2020; 6 (15): eaaw0158
Mesenchymal stromal cells (MSCs) modulate immune cells to ameliorate multiple inflammatory pathologies. Biophysical signals that regulate this process are poorly defined. By engineering hydrogels with tunable biophysical parameters relevant to bone marrow where MSCs naturally reside, we show that soft extracellular matrix maximizes the ability of MSCs to produce paracrine factors that have been implicated in monocyte production and chemotaxis upon inflammatory stimulation by tumor necrosis factor-α (TNFα). Soft matrix increases clustering of TNF receptors, thereby enhancing NF-κB activation and downstream gene expression. Actin polymerization and lipid rafts, but not myosin-II contractility, regulate mechanosensitive activation of MSCs by TNFα. We functionally demonstrate that human MSCs primed with TNFα in soft matrix enhance production of human monocytes in marrow of xenografted mice and increase trafficking of monocytes via CCL2. The results suggest the importance of biophysical signaling in tuning inflammatory activation of stromal cells to control the innate immune system.
View details for DOI 10.1126/sciadv.aaw0158
View details for Web of Science ID 000525751400002
View details for PubMedID 32284989
View details for PubMedCentralID PMC7141831
Chapter 1 - Design principles for dynamic microphysiological systems
Microfluidic Cell Culture Systems
Elsevier Inc.. 2019; 2: 1–29
View details for DOI 10.1016/B978-0-12-813671-3.00001-3
Community health workers on a college campus: Effects on influenza vaccination
JOURNAL OF AMERICAN COLLEGE HEALTH
2018; 66 (4): 317–23
To assess the impact of a campus community health worker program (HealthPALs) on student influenza vaccination.Undergraduate students at a northeastern US university (enrollment 6650), influenza seasons 2011-2012 through 2015-2016.Study design: Difference-in-differences analysis of student vaccination at campus dormitory influenza clinics during intervention vs. baseline.In the first intervention year, HealthPALs conducted in-person peer outreach at several campus dormitory flu clinics. Subsequent years, HealthPALs conducted an enhanced intervention, with the addition of a personalized, dormitory-specific social media campaign appealing to students' community identity.The initial intervention increased vaccinations by 66% (IRR = 1.66, 95%CI 1.39-1.97) at intervention clinics relative to control. The enhanced intervention increased vaccinations by 85% (IRR = 1.85, 95%CI 1.75-1.96).Community health workers can be a highly effective, low-cost strategy for increasing influenza vaccination among college students. This model could also be used to address other campus health challenges where student engagement is key.
View details for PubMedID 29447623
Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery.
2017; 16 (2): 236-243
Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel's mechanical properties. Here, we report a microfluidic-based method for encapsulating single cells in an approximately six-micrometre layer of alginate that increases the proportion of cell-containing microgels by a factor of ten, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that, for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.
View details for DOI 10.1038/nmat4781
View details for PubMedID 27798621
View details for PubMedCentralID PMC5372217