Using reprogramming to model diseases of the human brain
Reprogramming somatic cells to induced pluripotent stem (iPS) cells and directed differentiation opens up for in vitro studies of neurons from patients. The Falk group is focusing on questions in early human neurogenesis:
- How do neural stem cells decide between self-renewal and differentiation? How are these decisions hampered in neurodevelopmental disorders? How are impaired neural stem cell proliferation, differentiation and migration resulting in less functional neurons?
- Are in vitro human neurogenesis, migration and maturation in 2D and/or 3D systems mimicking development in health and disease?
To answer these questions we are building cellular models of the healthy and diseased human brain using reprogrammed patient cells. We derive patient specific iPS cells that are further differentiated into patient specific neuroepithelial stem (NES) cells. Both iPS and NES cell lines can be robustly expanded in culture and by applying efficient neuronal differentiation protocols we derive close to pure cultures of unlimited numbers of neurons for our studies. We use these cellular models to study proliferation, self-renewal, and differentiation potential as well as the function and subtype of derived neurons to uncover disease mechanisms.
A human patient iPS cell colony stained for pluripotency markers Oct4 in green and Tra1-81 in red.
Photo M. Shahsavani.
Spider silk for xeno-free long-term self-renewal and differentiation of human pluripotent stem cells.
Biomaterials 2014 Oct;35(30):8496-502
A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons.
Biomaterials 2014 Feb;35(5):1420-8
Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.
J. Neurosci. 2013 Jul;33(30):12407-22
Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell-derived long-term self-renewing neuroepithelial-like stem cells.
Stem Cells 2012 Jun;30(6):1163-73
Anna Falk - PI
Mansoureh Shahsavani - PhD student
Anders Lundin - PhD student
Ana Marin Navarro - PhD student
Matti Lam - PhD student
Robin Pronk - PhD student
Elias Uhlin - PhD student
Malin Kele - Senior lab manager
Ronny Falk - Senior lab manager
Jahan Salma - Postdoc
Mohsen Moslem - Postdoc
Kelly Day - Research assistant
Harriet Rönnholm - Research assistant