August 5, 2020

The Niche

Knoepfler lab stem cell blog

OCT4-SOX DNA dance, PRC2, a noisy competition & more cell weekly reads

What’s new in the stem cell, cell therapy, and regenerative medicine world as well as biomedical science more generally including cancer?

There’s quite a bit of news as reflected in media pieces and new pubs. Today’s post is focused on pubs that just came out.

For last week’s recommended reads see here.

Oct4-Sox2 Nucleosome Binding & Impact in mESCs

This is one of my favorite papers of 2020 so far, coming to us from ScienceMechanisms of OCT4-SOX2 motif readout on nucleosomes. I knew from the title I was going to be into this one! When I was a grad. student my work was mostly focused on DNA binding by homeodomain proteins, in particular Pbx family members and Hox proteins, but also the oncogenic fusion protein E2A-Pbx1. I always wondered how they would impact the nucleosome and potentially histone modifications. Now we have more insights into this kind of question for Oct4 and Sox2, which do impact the nucleosome. The bigger picture take-home is “This analysis reveals position-dependent binding modes that were validated in vivo, providing insights on how transcription factors read out chromatinized motifs.”

PRC2 needs RNA in a stem cell context

Nature Genetics. RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells. This is a great new paper from the Thomas Cech group. It feels like there’s a vast amount to still learn about PRC2 and how it works on chromatin. One powerful method used here on IPSCs is RNA-dependent ChIP-Seq or rChIP-Seq. Throwing RNAse A into the mix, you can define interactions that are RNA dependent and independent.

EMBO J 2020 Fig 3b Salazar-Roa stem cells
“miR‐203‐exposed human iPSCs efficiently contribute to human–mouse interspecies chimeras” EMBO J 2020 Fig 3b Salazar-Roa et al.

miRNA and stem cell differentiation

Embo J. Enhancing pluripotent stem cell differentiation via miRNA.Transient exposure to miR‐203 enhances the differentiation capacity of established pluripotent stem cells. See data above in their Fig. 3b showing miR-203 somehow boosts interspecies chimerism.

Base-editing the mitochondrial genome

A Nature overview piece Mitochondrial genome editing gets precise covers a step forward in fixing mitochondrial genome. Here’s the actual Nature research article: A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Can this be translated to address mitochondrial diseases?

Risks of GvHD after allo transplant and role of gut goblet cells

Science Translational Medicine. Getting someone else’s stem cells is sometimes portrayed as low-risk or even risk free by some proponents of a more relaxed framework for stem cell injections, but there are real risks. The most prominent is GvHD. This new paper zeroes in on how an animal (mice) receiving someone else’s stem cells can lead to GvHD and how goblet cells may be key players. Intestinal goblet cells protect against GVHD after allogeneic stem cell transplantation via Lypd8.  This was primarily a mouse study but also used human biopsy specimens.

Goblet cells are mucous-producing single-cell glands, in this case in the intestine, a hot spot during GvHD. For more on the risk of GvHD in stem cell injection recipients who go to unproven clinics see here.

Adult glioma invoke a neurodevelopmental program

Nature Communications. Nice single-cell mapping study, role for cancer stem cells, and some familiar neural transcription factors. Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy

A noisy stem cell competition

PNAS. How random is lineage commitment and survival? Stem cell lineage survival as a noisy competition for niche access. Lots of movies in this one so get the popcorn, although mostly of colored squares used in modeling. This kind of area also gets back to how random different phases of reprogramming are to make IPS cells. Random and then orderly?

Fat stem cells for breast augmentation

John D. Gearhart, stem cell biologist, stem cells
John D. Gearhart, stem cell biologist.

Stem Cells Translational Medicine. For years clinics have sold the idea of using fat stem cells to aid in breast augmentation and reconstruction, but these companies did not have data to back that up.

A new study provides some of the first rigorous evidence that compared to fat transfer alone (fat transferred from another part of the body can be used for breast augmentation instead of silicon implants) fat plus adipose stem cells yielded substantially better results.

This was a small, but randomized controlled study.

The paper was entitled, Ex vivo‐expanded autologous adipose tissue‐derived stromal cells ensure enhanced fat graft retention in breast augmentation: A randomized controlled clinical trial.

An important thing to note is that both fat stem cell products and fat tissue combined with those cells are likely considered drugs from an FDA perspective so doctors cannot just start selling this kind of thing without being careful about it.

And a loss for the stem cell field

John D. Gearhart, pioneering Hopkins and University of Maryland stem cell scientist, dies. Sometimes I think us scientists just assume our colleagues are immortal and will go on doing research forever, but of course that’s not the case for any of us. Gearhart died after a long battle with gastric cancer.

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