Recommended reads: stem cells on the brain, heart, COVID

There are weeks when it seems like papers on stem cells keep popping up. It can be a challenge to keep up with reading all the papers you want to read. Other times it is cell biology news that keeps breaking. The big news of the past week or so was unfortunately the concerning development on the halt of BlueBird Bio’s gene therapy trial for sickle cell.

Here are the many papers of this week that struck me as interesting.

Brain stem cell maintenance in mice and Ascl1

Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population, Cell Stem Cell. There is an ongoing debate about stem cells in the adult human brain, but it seems clearer that adult mice still have stem cells and ongoing neurogenesis in their brains. This paper uses the mouse as a model to provide insights into adult brain stem cell programming and maintenance.

It’ll be interesting to see if this same normal Ascl1 mechanism described in the new paper is at work in people. The main data on Ascl1 is in Fig. 6, which is included above.

They report that Ascl1 may be the key factor that maintains stem cell populations in the aging mouse brain. My own lab reported in our new paper last summer that ASCL1 may be of particular importance downstream of mutant histone H3.3 in high-grade childhood gliomas.

Stem cells and the Heart

• SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function, Stem Cell Reports. This paper is from Chuck Murry’s group at the UW. We get some insights into how the virus that causes the COVID-19 disease can affect the heart
• Myofibrillar structural variability underlies contractile function in stem cell-derived cardiomyocytes, Stem Cell Reports.

Additional notable stem cell pubs

• Rbbp4 suppresses premature differentiation of embryonic stem cells, Stem Cell Reports. 
• Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells, Nature Communications.
• MSCs for COVID-19. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial, Signal Transduction and Targeted Therapy. Another umbilical cord MSCs for COVID-19 study. A January paper from University of Miami claimed some benefit, but with some sizable caveats including a very small study size and balance issues. Now this February paper also tends that positive way in tone even though in their own chosen outcome measures almost none were convincingly statistically significant. There were also some more adverse events in those given MSCs than placebo in some cases including 2 more severe adverse events versus none in the placebo group, although the authors stated, “The incidence of adverse events was similar in the two groups.”
• Formative pluripotent stem cells show features of epiblast cells poised for gastrulation, Cell Research.
• Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells, Scientific Reports. Onc201 is also being studied in high-grade childhood gliomas.
• Tissue damage induces a conserved stress response that initiates quiescent muscle stem cell activation, Cell Stem Cell.