Cell model of the brain provides new knowledge on developmental disease

September 19, 2017

By reprogramming skin cells into nerve cells, researchers at Karolinska Institutet in Sweden are creating cell models of the human brain. In a new study published in Molecular Psychiatry the researchers describe how cells from patients with the severe developmental disease lissencephaly differ from healthy cells. The method can provide vital new knowledge on difficult-to-study congenital diseases.

Lissencephaly is a rare congenital developmental disease that can be caused by, amongst other anomalies, a mutation of the DCX gene. Affected individuals are born with serious developmental disabilities and a brain that is smooth instead of folded.

The discovery that it is possible to reprogramme specialised cells such as skin cells in order to reverse their development back to stem cells was rewarded with the 2012 Nobel Prize. The resulting so-called iPS-cells (induced pluripotent stem cells) can then be turned into other specialised cell types.

Anna Falk, docent at Karolinska Institutet's Department of Neuroscience, uses this technique to build cell models of the human brain. In the present study, her team took skin cells from patients with lissencephaly and turned them into iPS cells, which they then cultivated under special conditions into neuronal stem cells and neurons that are copies of those in the patients' brains.

By examining the cell cultivation dishes, the researchers were able to observe how the patients' cells behaved and developed from stem cells to nerve cells and compare them with cells from healthy controls. They found that the diseased cells matured much more slowly, sent out shorter projections and were much less mobile.

"It's already known that DCX affects the ability of neurons to migrate, but we can now show that DCX plays a much greater, broader part in brain development than that," says Dr Falk. "Our hypothesis is that it's this, the damaged nerve cells' resistance to maturation that causes the disease."

Since there are no relevant animal models for lissencephaly, the reprogramming technique has been essential to the study of lissencephaly's underlying pathogenesis. At Dr Falk's laboratory, the method is used to also study other congenital diseases that affect the brain, such as autism and Down syndrome. In future projects, the researchers hope to study how diseased cells can be modified to act as healthy cells.

"What many developmental diseases have in common seems to be the failure of brain cells to mature at the same rate as they do in healthy people," says Dr Falk. "Trying to influence the cells so that they behave like healthy cells is the first step towards some kind of therapy for these diseases."
-end-
The study was a collaboration with Karolinska University Hospital, Uppsala University, SciLifeLab and the Salk Institute for Biological Studies in the USA. It was financed by several bodies, including the Swedish Foundation for Strategic Research, the Åke Wiberg Foundation, the Tore Nilson Foundation, the Jeansson Foundations, the Thuring Foundation and the Swedish Research Council, and through the KID and SFO funding schemes.

Publication: "An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis". M Shahsavani, R Pronk, R Falk, M Lam, M Moslem, S Linker, J Salma, K Day, J Schuster, B-M Anderlid, N Dahl, FH Gage, A Falk. Molecular Psychiatry, online 19 September 2017, doi: 10.1038/MP.2017.175

Karolinska Institutet

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.