My lab is focused in part on chromatin states in stem cells and cancer including heterochromatin. In fact, my lab’s website is chromatin.com. Heterochromatin is dense, often inactive chromatin. By H&E staining and electron microscopy, heterochromatin looks dark compared to the rest of the nucleus, largely composed of euchromatin.
Toward the end of my postdoc at The Hutch I found that loss of myc in neural stem cells leads to more heterochromatin. See the image below.
We also study the histone variant H3.3 so a new preprint on both H3.3 and chromatin is right up our alley. Let’s start with that.
Chromatin and heterochromatin
- Heterochromatin spreading in cancer cells through HDAC7 mediated histone H3.3 landscape reprogramming, BioRxiv.
- H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cells, Cell Rep.
- Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis, Nat. Gen.
- Decoding chromatin states by proteomic profiling of nucleosome readers, Nature.
Other reads
- FDA allowed Mesoblast to proceed with their BLA on their investigational cell therapy for GvHD. Hopefully this signals some more good news coming down the road but it’s been a tough path.
- In the continuing saga of trying and not succeeding in finding clinical uses for umbilical cord cells outside of their proven use for reconstitution, we have this: A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke, Stem Cells Transl Med. The team led by Joanne Kurtzberg found no benefit of cord cells for stroke, although the study was noted as incomplete in a sense due to enrollment issues. I have had concerns for years about Kurtzberg’s team at Duke requiring large payments like $15,000 from families for unproven cord cells for autism and CP via compassionate use. This continued even after the team itself found largely negative data on cord cells for autism. The Duke autism expanded access program recently ended without a good explanation.
- To Live Past 100, Mangia a Lot Less: Italian Expert’s Ideas on Aging, NYT. This is another one of those researcher profiles in the anti-aging space that needs more depth. It’s more of a lifestyle feature piece than a science or medicine piece that gets into actual data. It’s disappointing in many ways. Notably, it doesn’t mention the recent AHA abstract that noted higher risk of cardiovascular disease with intermittent fasting. The AHA abstract may have its own issues but it certainly points to potential risks of fasting. A lot probably depends on the health condition of the people in the study and what they eat when they aren’t fasting. Was it relatively unhealthy food post-fast?
- Brain-cell transplants are the newest experimental epilepsy treatment Neurona Therapeutics’ epilepsy treatment could be a breakthrough for stem-cell technology, MIT Tech Review. Since the trial only has 5 people, I’d say Antonio was a little too excited in this piece, but I agree this area is promising and the tech is cool. I also am hopeful on Neurona Therapeutics and its cell therapy approach to epilepsy but it’s fairly early days.
Hey Paul,
So correct me if I’m wrong but from what I understand umbilical cord blood is largely comprised of hematopoietic stem cells (HSCs). From understand there are only a few mesenchymal stem cells in umbilical cord blood. Mesenchymal stem cells are typically harvested from umbilical cord tissue, not umbilical cord blood.
And this study used umbilical cord blood, so this study did not use umbilical cord “tissue derived” mesenchymal stem cells.
Little tid bit from the study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872695/
It is also possible that other cellular products derived from cord blood, cord tissue, or placenta, could improve functional outcomes after stroke. These include ex vivo expanded cord blood monocytes, DUOC—an expanded cord blood macrophage capable of inducing remyelination in early phase clinical trials, and cord tissue derived mesenchymal stromal cells (MSC) given intrathecally or intravenously. While these products are in development, none have been systematically studied in ischemic stroke. Banked cord blood, although, has the advantage of rapid availability in the acute stroke setting. Perhaps combination cellular therapy will ultimately be the best approach.
So yeah this study used “umbilical cord blood” which is just blood from the umbilical cord, which is different from umbilical cord mesenchymal stem cells.
Oh and check it out I have some exciting news to share. So Joanne Kurtzberg, who above ran the study on stroke using umbilical cord blood, she also conducted this placebo controlled phase 2 trial for autism in children using umbilical cord “tissue derived” mesenchymal stem cells. There were 137 participants so it was a pretty large trial. And if you follow this here link it shows that it’s been “completed” So I guess it’s done and they have yet to publish the results. I can’t wait to see the results, I’ve had my eye on this trial for a couple of years now. I’m hoping the results are world changing. I got my fingers crossed.
https://classic.clinicaltrials.gov/ct2/show/NCT04089579?term=Marcus+foundation&cntry=US&sort=nwst&draw=2&rank=9