In two recently published papers, a scientific reports on the discovery and implementation of a new, more efficient method for generating an important brain stem cell in the laboratory. The studies were published in Nature Communications and Stem Cell Reports.
“Making these specialized brain stem cells on a large scale at high purity from pluripotent stem cells gives us a powerful tool to study previously inaccessible normal and diseased tissues in the central nervous system,” said the senior author of the two papers. “We applied our technology to genetic models of myelin disease, which resulted in the discovery of a chemical compound that helps diseased myelin-producing cells to survive.”
Myelin, a fatty substance produced by cells called oligodendrocytes, coats nerve fibers and enables electrical signaling in the brain and facilitates normal neurological function.
Induced pluripotent stem cells are master cells that can potentially produce any cell the body needs. They are generated directly from existing adult cells. Embryonic stem cells are also pluripotent.
As reported in Nature Communications, researchers developed a new methodology to generate large quantities of oligodendrocytes and their progenitor cells—known as oligodendrocyte progenitor cells or OPCs—from mouse embryonic stem cells and induced pluripotent stem cells.
Many genes and cellular processes have been associated with oligodendrocyte dysfunction, but scientists have typically needed to make mutant mice to investigate these processes, often involving expensive, multi-year studies to examine a single aspect of this biology. To address this problem, the team developed a rapid and highly efficient method for generating OPCs and oligodendrocytes from pluripotent stem cells from any genetic background—providing new access to these relatively inaccessible brain cells in healthy and diseased states.
In Stem Cell Reports, the researchers leveraged this OPC generation technology to provide new insights and therapeutic strategies for a fatal genetic disorder of myelin, Pelizaeus Merzbacher disease (PMD). The team found that there was an unexpectedly early critical phase in PMD-affected cells characterized by endoplasmic reticulum stress and cell death as OPCs exit their progenitor state.
The endoplasmic reticulum is the part of the cell involved in the processing of protein. In PMD, which almost exclusively affects male children, oligodendrocytes are lost and myelin is not properly formed in the brain and spinal cord. Due to their diseased myelin, children with PMD exhibit often-debilitating problems of coordination, motor skills, verbal expression and learning. Due to the disease’s severity, patients typically die before adulthood.
To overcome this early cell death in PMD cells, the team screened thousands of drug-like compounds and found that one, known as Ro 25-6981, was especially successful in rescuing the survival of PMD oligodendrocytes in mouse and human cells in the laboratory and in PMD mice.
The team’s findings have implications beyond PMD. Numerous neurological and psychiatric diseases are characterized by myelin loss or dysfunction, including multiple sclerosis, spinal cord injury and schizophrenia. Measures to regenerate or restore myelin could offer patients hope in these and numerous other disorders affecting the brain and spinal cord.
https://thedaily.case.edu/cwru-research-new-method-more-efficiently-generate-brain-stem-cells/
https://www.nature.com/articles/s41467-018-06102-7
https://www.sciencedirect.com/science/article/pii/S2213671118303205
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fchemical-screening&filter=22
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Frapid-functional&filter=22
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
Repairing muscle injury and disease with stem cells
Read more
How NANOG turns on human cell pluripotency
Read more
Sleep deprivation impairs stem cells in the cornea
Read more
The development of tear duct organoids
Read more
Transcription factors control hematopoietic stem cell niche by inhi…
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