Bio links, Fall 2025

I’d like to highlight some biological news that recently came out:

ImputePGTA from Herasight: estimating an embryo’s genotype based on very low coverage sequencing (as low as 70,000 reads, or ∼0.002x coverage!) given knowledge of the phased whole genome sequences of the embryo’s parents. Haplotype phasing is most effective if the embryo’s grandparents have also been sequenced. Since many IVF clinics offer PGT-A but not PGT-P, this will expand the number of people able to use polygenic embryo selection.

Generation of modified cows and sheep from spermatid-like haploid embryonic stem cells (unfortunately paywalled, but very cool!). These researchers made androgenetic1 stem cells by removing egg chromosomes and inserting sperm. These cells can be used for genome engineering, and subsequently inserted into an egg to fertilize it. This method would likely work in humans too (with some optimization required), although it could only produce female offspring because an X chromosome is essential in haploid stem cells.

Designing protein-based artificial kinetochores as decoys to prevent meiotic errors in oocytes. Aged oocytes lose chromosome cohesion which can lead to aneuploid embryos. These researchers developed an artificial system to reduce premature separation of chromosomes. Excitingly, in mouse oocytes this suppresses age-associated aneuploidy. (Previous research in this area from Melina Schuh’s group has focused on artificial cohesins, but this kinetochore approach is also quite promising.)

Induction of experimental cell division to generate cells with reduced chromosome ploidy. The Mitalipov lab put skin cell nuclei into human eggs and stimulated them to divide in a process called “mitomeiosis”. The cells distributed their chromosomes randomly, on average ending up with half the usual copy number. When fertilized with sperm, this could sometimes form blastocysts, but they were highly aneuploid. I will have more comments on this in a future post which I am currently drafting. Overall it is similar to their previous research in mice (which I covered in a post last year), but modified to work for humans now. I encourage people who are interested in this to read the actual paper (which is pretty cool), not the popular media coverage (which is less accurate).

Ovarian development is driven by early spatiotemporal priming of the coelomic epithelium. This preprint combines existing datasets to make a detailed developmental atlas of the mouse ovary, and identifies mechanisms of supporting cell formation.

3D Mapping of Intact Ovaries Reveals the Aging Dynamics of the Ovarian Reserve. A method for whole-ovary imaging (again, with mouse ovaries) characterizes the sizes and spatial distribution of oocytes. We have been doing similar things at Ovelle, but not with mice.

Morphogen gradients applied basally to human embryonic stem cells to control and dissect tissue patterning. A microfluidic device creates defined concentration gradients of morphogens (in this case, BMP4), allowing for reproducible patterning of stem cell differentiation.

Self-amplifying RNA enables rapid, durable, integration-free programming of hiPSCs. Directed differentiation of stem cells to neurons through self-amplifying RNA encoding the NGN2 transcription factor.

Generative Design of Cell Type-Specific RNA Splicing Elements for Programmable Gene Regulation. Remember my post about laser sharks (sorry, I mean cell type specific regulatory DNA elements)? This paper did that for RNA splicing. It’s pretty cool.

A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording. From the Shendure lab, characterization of tools for design of efficient CRISPR-based genetic circuits.

Ever since starting my herpesvirus post series I’ve taken an interest in these pathogens. It’s underappreciated how bad they are. Most people view them as merely inconvenient, but they actually cause a ton of bad stuff. If I wasn’t researching oogenesis, I’d probably be trying to develop antiviral technology.

Moderna’s cytomegalovirus vaccine fails phase 3 trial. A big setback in the fight against CMV. I’m not aware of any other vaccine efforts that show any promise.

Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus. EBV, previously known to cause multiple sclerosis, is now established as a cause of lupus. These gosh-darn viruses keep causing trouble!