It is now possible to reprogram cells from the liver into the precursor cells that give rise to the pancreas by altering the activity of a single gene. A team of researchers have now accomplished this feat in mice. Their results should make it feasible to help diabetic patients through cell therapy.
In patients suffering from type I diabetes, their immune system turns against their own bodies and destroys a type of pancreatic cell called islet cells. Without these cells, the pancreas is unable to produce the hormone insulin and blood glucose rises, which leads to diabetic disease. At that point, such patients need to inject insulin for the rest of their lives.
A way to provide a lasting help to the afflicted may be to grow new pancreatic cells outside of the body. The team has now succeeded in thrusting liver cells into an "identity crisis" -- in other words, to reprogram them to take on a less specialized state -- and then stimulate their development into cells with pancreatic properties.
A gene called TGIF2 plays a crucial role in the process. TGIF2 is active in the tissue of the pancreas but not in the liver. For the current study a graduate student tested how cells from mouse liver behave when they are given additional copies of the TGIF2 gene.
Hepatocytes expressing Tgif2 undergo extensive transcriptional remodelling, which represses the original hepatic identity and, over time, induces a pancreatic progenitor-like phenotype. Consistently, in vivo forced expression of Tgif2 activates pancreatic progenitor genes in adult mouse hepatocytes.
The researchers transplanted the modified cells into diabetic mice. Soon after this intervention, the animals' blood glucose levels improved, indicating that the cells indeed were replacing the functions of the lost islet cells. The results bring cell therapies for human diabetic patients one step closer to reality.
This study uncovers the reprogramming activity of TGIF2 and suggests a stepwise reprogramming paradigm, whereby a ‘lineage-restricted’ dedifferentiation step precedes the identity switch.
The obvious next step is to translate the findings from the mouse to humans. The lab is currently testing the strategy on human liver cells in a project funded in 2015 by the European Research Council. "There are differences between mice and humans, which we still have to overcome," senior author says. "But we are well on the path to developing a 'proof of concept' for future therapies."
Latest News
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Addressing both flu and COV…
By newseditor
Posted 26 Mar
How the brain senses body p…
By newseditor
Posted 26 Mar
Other Top Stories
New insights into the molecular basis of memory
Read more
Scientists manipulate consciousness in rats
Read more
Researchers map brain connections that regulate homeostasis
Read more
Improving brain's garbage disposal may slow Alzheimer's disease
Read more
Algorithms, apps to understand Alzheimer's, brain maps
Read more
Protocols
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Profiling native pulmonary…
By newseditor
Posted 08 Mar
Publications
Integrated plasma proteomic…
By newseditor
Posted 27 Mar
APP antisense oligonucleoti…
By newseditor
Posted 27 Mar
Targeting Erbin-mitochondri…
By newseditor
Posted 27 Mar
Regulation of Zbp1 by miR-9…
By newseditor
Posted 27 Mar
Pain-free oral delivery of…
By newseditor
Posted 27 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar