Biology textbooks teach us that adult cell types remain fixed in the identity they have acquired upon differentiation. By inducing non-insulin-producing human pancreatic cells to modify their function to produce insulin in a sustainable way, researchers show for the first time that the adaptive capacity of our cells is much greater than previously thought. Moreover, this plasticity would not be exclusive to human pancreatic cells. A revolution for cell biology, to be discovered in the journal Nature.
The human pancreas harbors several types of endocrine cells (α, β, δ, ε and &Upsih;) that produce different hormones responsible for regulating blood sugar levels. These cells are bundled into small clusters, called pancreatic islets or islets of Langerhans. Diabetes occurs when, in the absence of functional β cells, blood sugar levels are no longer controlled. The team had already demonstrated, in mice, that the pancreas has the ability to regenerate new insulin cells through a spontaneous mechanism of identity change of other pancreatic cells. But what about the human being? Moreover, is it possible to artificially promote this conversion?
To explore whether human cells have this ability to adapt, the scientists used islets of Langerhans from both diabetic and non-diabetic donors. They first sorted the different cell types to study two of them in particular: α cells (glucagon producers) and &Upsih; cells (pancreatic polypeptide cells). "We divided our cells into two groups: one where we introduced only a fluorescent cell tracer, and the other where, in addition, we added genes that produce insulin transcription factors specific to β cells," explains the senior author.
The researchers then reconstructed "pseudo-islets", with only one cell type at a time to accurately study their behavior. "First observation: the simple fact of aggregating cells, even into monotypic pseudo-islets, stimulates the expression of certain genes linked to insulin production, as if the "non-β" cells naturally detected the absence of their "sisters". However, in order for the cells to start producing insulin, we had to artificially stimulate the expression of one or two key β cell genes," says the first author of this work. One week after the experiment began, 30% of the α cells were producing and secreting insulin in response to glucose. &Upsih;-Cells, under the same treatment, were even more effective and numerous in converting and secreting insulin in response to glucose.
In a second step, the researchers transplanted these monotypic pseudo-islets of modified human α cells into diabetic mice. "Human cells proved to be very effective. The mice recovered!" rejoices the senior author. "And as expected, when these human cell transplants were removed the mice became diabetic again. We obtained the same results with cells from both diabetic and non-diabetic donors, showing that this plasticity is not damaged by the disease. In addition, this works in the long term: six months after transplantation, the modified pseudo-islets continued to secrete human insulin in response to high glucose."
A detailed analysis of these human glucagon cells that have become insulin producers shows that they retain a cell identity close to that of α cells. Autoimmune diabetes, or type 1 diabetes, is characterized by the destruction of β cells by the immune system of patients. The researchers then wondered whether these modified α cells would also be targeted by autoimmunity, since they remain different from β-cells. To test their resistance, they co-cultured them with T cells from patients with type 1 diabetes. "We found that modified α cells triggered a weaker immune response, and therefore might be less likely to be destroyed than native β cells."
Today, pancreas transplantation is performed in cases of extremely severe diabetes, by transplanting either the entire pancreas or, preferably, only pancreatic islets, a much less invasive approach. This technique is very effective, but has its limits: like any transplant, it goes hand in hand with immunosuppressive treatment. Despite this, the transplanted cells disappear after a few years. "The idea of using the intrinsic regenerative capacities of the human body makes sense here," the senior author emphasizes. However, many hurdles remain before a treatment resulting from our discovery can be proposed. "We must indeed find a way - pharmacological or by gene therapy - to stimulate this change of identity in the cells concerned within the patient's own pancreas, but without causing adverse effects on other cell types" the author adds. The road will be difficult and long.
https://www.nature.com/articles/s41586-019-0942-8
Human pancreatic alpha cells changed to produce insulin!
- 1,448 views
- Added
Edited
Latest News
Circadian rhythms can influ…
By newseditor
Posted 27 Apr
With hybrid brains, these m…
By newseditor
Posted 27 Apr
Blocking activation of NF-κ…
By newseditor
Posted 27 Apr
Vitamin D regulates microbi…
By newseditor
Posted 27 Apr
Role of alternative splicin…
By newseditor
Posted 27 Apr
Other Top Stories
Modern diets and gut microbiome composition
Read more
Zika virus found in tears
Read more
Newborn gut microbiome predicts later allergy and asthma
Read more
Tuberculosis and HIV coinfection
Read more
How insect-borne viruses 'suppress' the immune system to cause disease
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Single dose creatine improv…
By newseditor
Posted 27 Apr
Autonomous circadian rhythm…
By newseditor
Posted 27 Apr
Functional sensory circuits…
By newseditor
Posted 27 Apr
Positive selection CRISPR s…
By newseditor
Posted 27 Apr
Focal clusters of peri-syna…
By newseditor
Posted 27 Apr
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