Mechanisms underlying direct programming of stem cells could eventually lead to cell-replacement therapies
A team of scientists has uncovered details of the cellular mechanisms that control the direct programming of stem cells into motor neurons. The scientists analyzed changes that occur in the cells over the course of the reprogramming process. They discovered a dynamic, multi-step process in which multiple independent changes eventually converge to change the stem cells into motor neurons.
āThere is a lot of interest in generating motor neurons to study basic developmental processes as well as human diseases like ALS and spinal muscular atrophy,ā said Shaun Mahony, assistant professor of biochemistry and molecular biology at Penn State and one of the lead authors of the paper. āBy detailing the mechanisms underlying the direct programing of motor neurons from stem cells, our study not only informs the study of motor neuron development and its associated diseases, but also informs our understanding of the direct programming process and may help with the development of techniques to generate other cell types.ā
The direct programming technique could eventually be used to regenerate missing or damaged cells by converting other cell types into the missing one. The research findings, which appear online in the journal Cell Stem Cell on December 8, 2016, show the challenges facing current cell-replacement technology, but they also outline a potential pathway to the creation of more viable methods.
āDespite having a great therapeutic potential, direct programming is generally inefficient and doesnāt fully take into account molecular complexity,ā said Esteban Mazzoni, an assistant professor in New York Universityās Department of Biology and one of the lead authors of the study. āHowever, our findings point to possible new avenues for enhanced gene-therapy methods.ā
The researchers had shown previously that they can transform mouse embryonic stem cells into motor neurons by expressing three transcription factors — genes that control the expression of other genes — in the stem cells. The transformation takes about two days. In order to better understand the cellular and genetic mechanisms responsible for the transformation, the researchers analyzed how the transcription factors bound to the genome, changes in gene expression, and modifications to chromatin at 6-hour intervals during the transformation.
āWe have a very efficient system in which we can transform stem cells into motor neurons with something like a 90 to 95 percent success rate by adding the cocktail of transcription factors,ā said Mahony. āBecause of that efficiency, we were able to use our system to tease out the details of what actually happens in the cell during this transformation.ā
āA cell in an embryo develops by passing through several intermediate stages,ā noted Uwe Ohler, senior researcher at the Max DelbrĆ¼ck Center for Molecular Medicine (MDC) in Berlin and one of the lead authors of the work. āBut in direct programming we don’t have that: we replace the gene transcription network of the cell with a completely new one at once, without the progression through intermediate stages. We asked, what are the timing and kinetics of chromatin changes and transcription events that directly lead to the final cell fate?”
The research team found surprising complexity — programming of these stem cells into neurons is the result of two independent transcriptional processes that eventually converge. Early on in the process, two of the transcription factors — Isl1 and Lhx3 — work in tandem, binding to the genome and beginning a cascade of events including changes to chromatin structure and gene expression in the cells. The third transcription factor, Ngn2, acts independently making additional changes to gene expression. Later in the transformation process, Isl1 and Lhx3 rely on changes in the cell initiated by Ngn2 to help complete the transformation. In order for direct programming to successfully achieve cellular conversion, it must coordinate the activity of the two processes.
āMany have found direct programming to be a potentially attractive method as it can be performed either in vitro — outside of a living organism — or in vivo — inside the body and, importantly, at the site of cellular damage,ā said Mazzoni. āHowever, questions remain about its viability to repair cells — especially given the complex nature of the biological process. Looking ahead, we think itās reasonable to use this newly gained knowledge to, for instance, manipulate cells in the spinal cord to replace the neurons required for voluntary movement that are destroyed by afflictions such as ALS.ā
Learn more:Ā How to Make a Motor Neuron
[osd_subscribe categories=’stem-cells’ placeholder=’Email Address’ button_text=’Subscribe Now for any new posts on the topic “STEM CELLS”‘]
Receive an email update when we add a new STEM CELLSĀ article.
The Latest on: Stem cells
[google_news title=”” keyword=”stem cells” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Stem cells
- 24 hours with ‘RHONY’ alum Kelly Bensimon: Stem cell facials, smoothies and a luxe $13M real estate touron May 11, 2024 at 4:43 pm
From catching up over coffee at her favorite hotel to luxurious facials from her go-to stem cell specialist to sipping trendy smoothies, the model-turned-mogul gave us an inside look at life in ...
- Ask the doctors: Stem cells from baby teeth must be carefully extractedon May 11, 2024 at 6:12 am
And now come the caveats. Stem cells can only be extracted from freshly removed teeth. This includes teeth that come out naturally and those that have been extracted. The baby teeth that some parents ...
- University Hospitals first in Northeast Ohio to offer outpatient stem cell therapieson May 10, 2024 at 3:20 pm
The UH Seidman Cancer Center started the program a year ago and modeled it after other programs around the country that have been active for nearly a decade.
- ERR-gamma 'trains' stomach stem cells to become acid-producing cellson May 10, 2024 at 8:00 am
Common conditions such as indigestion and heartburn as well as peptic ulcers, autoimmune gastritis and stomach and esophageal cancers have one thing in common—they involve disruptions of the normal ...
- The CDC issues a report about infections from stem-cell treatments in Mexicoon May 9, 2024 at 5:54 pm
The U.S. Centers for Disease Control and Prevention has issued a report about three cases of infections apparently linked to stem-cell treatments American patients received in Mexico ...
- Stem cells: A new mechanical transduceron May 9, 2024 at 4:59 pm
Scientists reveal how ETV4 controls stem cell differentiation in response to mechanical cues. Professor Jiwon Jang and Seungbok Yang, a PhD candidate, from the Department of Life Sciences at Pohang ...
- Stem Cell Injections in Mexico Led to Drug-Resistant Infectionson May 9, 2024 at 1:34 pm
Three patients developed difficult-to-treat Mycobacterium abscessus infections after receiving embryonic stem cell injections in Mexico in 2022, researchers reported. Two men -- o ...
- Stem cell treatments in Mexico linked to drug-resistant meningitis, joint infectionson May 9, 2024 at 12:35 pm
Antibiotic-resistant meningitis or severe, long-lasting joint infections: That's what three U.S. "medical tourists" brought home after seeking out unapproved stem cell treatments in Mexico, according ...
- Stem cell injections in Mexico can be hazardous. Report identifies US victims.on May 9, 2024 at 10:19 am
Two cases of bacterial infection shared identical genetic material even thought the procedures took place hundreds of miles apart.
via Bing News