Good news!
"Harvard stem cell biologists have discovered a way to grow the type of brain cells that degenerate in patients with amyotrophic lateral sclerosis (ALS) and suffer damage in spinal cord injuries.
In a paper published in the journal eLife, researchers engineered a cocktail of molecular signals to coax some “progenitor cells” — precursors that can differentiate into other cell types — to generate corticospinal neurons (CSNs), brain cells vital to voluntary motor control. ...
“.progenitor population is that it’s already distributed throughout the brain ... They’re sitting there — resident stem cells.”
The new study offers the first-ever model for growing corticospinal neurons in the lab, opening new windows for researching and potentially regenerating neurons for two devastating neurological afflictions. ..."
"eLife Assessment
This study presents fundamental new findings introducing a new approach for the reprogramming of brain glial cells to corticospinal neurons. The data is highly compelling, with multiple lines of evidence demonstrating the success of this new assay. These exciting findings set the stage for future studies of the potential of these reprogrammed cells to form functional connections in vivo and their utility in clinical conditions where corticospinal neurons are compromised."
From the abstract:
"Corticospinal neurons (CSN) centrally degenerate in amyotrophic lateral sclerosis (ALS), along with spinal motor neurons, and loss of voluntary motor function in spinal cord injury (SCI) results from damage to CSN axons.
For functional regeneration of specifically affected neuronal circuitry in vivo, or for optimally informative disease modeling and/or therapeutic screening in vitro, it is important to reproduce the type or subtype of neurons involved. No such appropriate in vitro models exist with which to investigate CSN selective vulnerability and degeneration in ALS, or to investigate routes to regeneration of CSN circuitry for ALS or SCI, critically limiting the relevance of much research. Here, we identify that the HMG-domain transcription factor Sox6 is expressed by a subset of NG2+ endogenous cortical progenitors in postnatal and adult cortex, and that Sox6 suppresses a latent neurogenic program by repressing proneural Neurog2 expression by progenitors.
We FACS-purify these progenitors from postnatal mouse cortex and establish a culture system to investigate their potential for directed differentiation into CSN. We then employ a multi-component construct with complementary and differentiation-sharpening transcriptional controls (activating Neurog2, Fezf2, while antagonizing Olig2 with VP16:Olig2).
We generate corticospinal-like neurons from SOX6+/NG2+ cortical progenitors and find that these neurons differentiate with remarkable fidelity compared with corticospinal neurons in vivo. They possess appropriate morphological, molecular, transcriptomic, and electrophysiological characteristics, without characteristics of the alternate intracortical or other neuronal subtypes. We identify that these critical specifics of differentiation are not reproduced by commonly employed Neurog2-driven differentiation. Neurons induced by Neurog2 instead exhibit aberrant multi-axon morphology and express molecular hallmarks of alternate cortical projection subtypes, often in mixed form. Together, this developmentally-based directed differentiation from cortical progenitors sets a precedent and foundation for in vitro mechanistic and therapeutic disease modeling, and toward regenerative neuronal repopulation and circuit repair."
Fig. 1 Identification and culture of SOX6+/NG2+ cortical progenitors with high purity and fidelity
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