Transdifferentiation towards expandable neural progenitors without rejuvenation as authentic cell model for age-associated neurodegenerative diseases
Description: Objectives:
We aim to invent a method to transdifferentiate human cells to proliferative neural progenitors that retain their donor’s age and hence represent authentic models for age-associated diseases.
Hypothesis:
Stem cell technologies enable the use of somatic cells from patients suffering from neurological diseases to study disease mechanisms and to explore treatment options. Current methods make use of induced pluripotent stem cells that represent rejuvenated embryonic cells with proliferative capacity or induced neurons that retain aging signature but lost the ability to divide. We hypothesize that primary human cells can be transdifferentiated towards dividing neural progenitors without rejuvenation.
Design and subjects:
We will establish assays to monitor the emergence of neural progenitors alongside cellular rejuvenation. Pools of smart mutagenesis libraries of selected transcription factors will be screened for variants that promote transdifferentiation without rejuvenation. Functions and phenotypes of induced neural progenitors will be evaluated to establish their capacity to model age-associated diseases.
Instruments: NA
Interventions: NA
Main outcomes measures:
We will develop a phenotypic readout that enables detection of transdifferentiated cells and their age signatures. The work will demonstrate that protein engineering can profoundly impact the trajectories of cell reprogramming experiments and identify enabling factors that facilitate the generation of proliferative neural progenitors without rejuvenation.
Data analysis: NA
Expected results:
The key deliverable will be a system for the selection of engineered factors that drive transdifferentiation without cellular rejuvenation leading to authentic cellular models for age-associated neurodegenerative diseases to unlock disease mechanisms and evaluate therapeutic strategies.
Funder: Health and Medical Research Fund
Amount: HKD 1,477,000
Funding type: grant
Funder scheme: HMRF - Advanced Medical Research
Start date: 2019-01-01
Investigator: RALF JAUCH
Institution: School of Biomedical Sciences, The University of Hong Kong
Funded outputs count: 6
Funder award ID: 08192886
OpenAlex ID: G856799431