Human Neuron Core

The Human Neuron Core operationalizes a new paradigm for disease modeling using human neurons derived from patients to support preclinical screening of potential drugs in a core facility aligned with a broad network of developmental neuroscience, neurology and stem cell expertise.

Services Provided: The Human Neuron Core provides two categories of service to investigators studying intellectual disability; one focuses on creating iPSC-derived neuron models of neurodevelopmental disorders and is managed by two PhD level supervisors with significant experience in stem cell biology. This is closely integrated with a second set of services managed by a PhD level supervisor with significant experience working with high-through screening equipment and miniaturization of cell based assays for drug screening. These services are further detailed below.

Human Neuron Differentiation and Phenotyping Services:

Assistant Directors: Pin-Fang (Ivy) Chen, PhD and Elizabeth Buttermore, PhD

  • Patient and unaffected control family member sample preparation for reprogramming to iPSCs from PBMCs or skin biopsy.
  • Coordinate reprogramming of patient samples to iPSC lines through the Harvard Stem Cell Institute iPSC core facility.
  • Characterization and expansion of iPSC lines for differentiation into neurons.  
  • Differentiation of human iPSC lines into specialized neuronal cell types using standardized operating protocols (SOPs).
  • Measures of spontaneous electrical activity from iPSC derived neurons using Axion Maestro Multi-electrode array platform.
  • Characterization of neuronal morphology using the ThermoFisher Arrayscan XTI.
  • To request core services, log into iLabs or contact the core:
  • https://childrenshospital.corefacilities.org/service_center/show_external/3496/human-neuron-differentiation-service-core

 

Assay Development and Drug Screening:

Assistant Director: Lee Barrett, PhD

  • Consultation and training for cell based assay development.

  • Consultation and access to small molecule libraries for screening campaigns.
  • Hourly fee-for-service access to research assistant to support screening campaigns.
  • Hourly fee-for-service access to high-throughput screening equipment. The core facility houses 2 high content screening platforms that include a Hamamatsu FDSS7000ex and a Thermofisher ArrayScan XTi, as well as a range of liquid handling equipment.
    • Hamamatsu FDSS7000EX kinetic reader has the capability of conducting measurements of fluorescence or luminescence in 384 wells at once, with time resolution of up to 40Hz. The equipment allows for measurements of changes in membrane potential and concentration of intracellular ions such as Ca2+ in primary cultures, stem cell-derived or trans-differentiated cells, or cell lines in a fast, accurate, parallel fashion.
    • ThermoFisher's Arrayscan XTI is an image based High Content Screening instrument that features a temperature and CO2 controlled live cell chamber to assay cell biology over several days. The Arrayscan XTI has an integrated liquid handler to administer compounds of interest, well by well, capturing changes in fluorescence up to 10Hz with an enhanced CCD camera and 7 LED light source using 6 to 384 well labware.
  • To request core services, log into iLABs or contact the core:
  • http://www.childrenshospital.org/research-and-innovation/research/cores/assay-development-and-screening-facility