Miguel Ramalho-Santos

Efficient stem cell-derived mouse embryo models for environmental studies Jorgensen, Bao, Junyent, et al. aggregate ESCs, TSCs, and PE-fated inducible GATA4-ESCs to build iGATA4-blastoids: robust and highly efficient stem cell models of the mouse blastocyst. iGATA4-blastoid...

Also noted: Efficient stem cell-derived mouse embryo models for environmental studies. www.cell.com/developmenta...

Stress controls heterochromatin inheritance via histone H3 ubiquitylation - Nature A histone ubiquitin-dependent regulatory hub governs stimulus-dependent heterochromatin propagation, with important implications for understanding mechanisms governing rapid changes in the epigen...

Discussed @mrsantosny.bsky.social lit review: Stress controls heterochromatin inheritance via histone H3 ubiquitylation. www.nature.com/articles/s41...

Development of the hematopoietic system: expanding the concept of hematopoietic stem cell-independent hematopoiesis Hematopoietic stem cells (HSCs) give rise to nearly all blood cell types and play a central role in blood cell production in adulthood. For many years it was assumed that these roles were similarly re...

As well as: Development of the hematopoietic system: expanding the concept of hematopoietic stem cell-independent hematopoiesis
www.cell.com/trends/cell-...

The Aorta‐Gonad‐Mesonephros (AGM): A Crossroads Between Hematopoiesis and Angiogenesis. A Historical Note The aorta-gonad-mesonephros (AGM) is a region of embryonic mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick, mouse, and human embryos. The AGM contain....

Also noted: The Aorta‐Gonad‐Mesonephros (AGM)- A Crossroads Between Hematopoiesis and Angiogenesis. A Historical Note
onlinelibrary.wiley.com/doi/10.1002/...

Cell-type-specific RNA polymerase II activity maps in intact tissues provide a gateway to mammalian gene regulatory mechanisms in vivo Chovatiya et al. developed PReCIS-seq, an in vivo approach that maps transcriptionally engaged RNA polymerase II in Cre-targeted cells within intact mouse tissues, without cell isolation. They report ...

Discussed @mrsantos.bsky.social lit review: Cell-type-specific RNA polymerase II activity maps in intact tissues provide a gateway to mammalian gene regulatory mechanisms in vivo.
www.cell.com/developmenta...

A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation - Nature Cell Biology The authors identify a chemical cocktail to generate totipotent-like cells, which they then use to build an embryo model. This model captures a developmental spectrum from early embryogenesis to post-...

Also noted:
A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation
www.nature.com/articles/s41...

Stabilizing a mammalian RNA thermometer confers neuroprotection in subarachnoid hemorrhage - Nature Communications Here the authors identify RNA G-quadruplexes as temperature-sensitive regulators of alternative splicing and gene expression, opening potential therapeutic avenues such as neuroprotection with potassi...

Discussed @mrsantos.bsky.social lit review: Stabilizing a mammalian RNA thermometer confers neuroprotection in subarachnoid hemorrhage. www.nature.com/articles/s41...

Single-cell susceptibility to viral infection is driven by variable cell states Not all cells that can be infected by a virus become infected with that virus. Single-cell clone tracing reveals intrinsic cell states with variable expression patterns that increase susceptibility to...

Also noted:
Single-cell susceptibility to viral infection is driven by variable cell states
www.cell.com/cell/abstrac...

Analog epigenetic memory revealed by targeted chromatin editing Cells store information by means of chromatin modifications that persist through cell divisions and can hold gene expression silenced over generations…

Discussed @mrsantos.bsky.social lit review: Analog epigenetic memory revealed by targeted chromatin editing. www.sciencedirect.com/science/arti...

Trick or Treat! 👻🎃

Single-cell nascent transcription reveals sparse genome usage and plasticity scFLUENT-seq is a single-cell method that sensitively captures nascent nuclear transcriptomes to reveal mRNA and ncRNA dynamics, heterogeneity across chromatin compartments, and transcriptional divers...

Also noted: Single-cell nascent transcription reveals sparse genome usage and plasticity www.cell.com/cell/abstrac...

Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although signaling circuits and gene regulatory networks that regulate pluripotent stem cell diffe...

Discussed @mrsantos.bsky.social lit review: Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells. www.biorxiv.org/content/10.1...

Maternal stress triggers early-life eczema through fetal mast cell programming - Nature Prenatal stress triggers molecular dysregulations in fetal neuroimmune circuits, leading to altered mast cell and sensory neuron function, which predisposes offspring to develop eczema in response to ...

Also noted: Maternal stress triggers early-life eczema through fetal mast cell programming. www.nature.com/articles/s41...

Preventing CpG hypermethylation in oocytes safeguards mouse development Kawamura et al. show that H3K36me2 removal by the KDM2A and KDM2B histone demethylases restricts DNMT3A in establishing global DNA methylation in oocytes. Maternal Kdm2a/Kdm2b knockout embryos die dur...

Discussed @mrsantos.bsky.social lit review: Preventing CpG hypermethylation in oocytes safeguards mouse development. www.cell.com/developmenta...

(4/4) Our findings redefine the role of TGF-β signaling in early development and suggest conserved parallels between embryonic diapause, stem cell quiescence, and cancer dormancy.

(3/4) Mechanistically, Smad2 represses the metabolic regulator Pparg, preventing lipid accumulation that is incompatible with dormancy. This links signaling, metabolism, and chromatin control during developmental pausing.

Nodal/Smad2 signaling sustains developmental pausing by repressing Pparg-mediated lipid metabolism Cells and organisms can enter transient dormant states to survive unfavorable conditions during development, physiological adult contexts, and disease. One paradigmatic case of dormancy is diapause, w...

(2/4) We discovered that Nodal/Smad2 signaling, a branch of the TGF-β pathway, is essential to sustain this paused state in embryonic stem cells and embryos. www.biorxiv.org/content/10.1...

(1/4) New Pre-print! 🌟
Embryonic development is usually seen as a continuous process, yet some embryos can pause their development to survive harsh conditions, a phenomenon known as diapause. How this pausing is actively maintained has remained a mystery.

2026 Election Nominations — International Society for Stem Cell Research Elections and nominations for the International Society for Stem Cell Research board of directors and officers.

The ISSCR is seeking nominations for Vice President and three Director positions. This is an opportunity to help shape the future of stem cell research and contribute to a global scientific community. Nominations are due 22 October 2025. Learn more 👉 https://www.isscr.org/nominations

John Gurdon was a true giant:
- founder of cell reprogramming;
- founder of molecular embryology;
- unabashed advocate for basic research;
- advisor to numerous successful trainees/PIs;
- gentle human that touched so many.
In dark times with science under attack, let his vision be a guiding light.

🚨 JOB ALERT 🚨
We are hiring TWO principal investigators in systems, cellular, chemical or molecular biology in Toronto, Canada at
@sinaihealth.bsky.social. We provide a generous startup, fully funded salary and academic appointment at U of Toronto.

Apply now or repost!

Thank you for this honor and the continued trust in our group's research! We hope that our work will honor the memory and legacy of Anne and Max Tanenbaum. It is truly a privilege to be part of the amazing communities of @uoftmedicine.bsky.social and @sinaihealth.bsky.social.

(4/4) These findings provide new insights on the chromatin-level regulation of MYC-driven breast cancer and uncover CHD1 as a novel synthetic lethal vulnerability and potential therapeutic target.

(3/4) We found that CHD1 is required to maintain an open chromatin landscape and a transcriptional program associated with cancer progression in MYC overexpressing breast cells and that this synthetic lethality may arise from nucleolar stress and p53 activation.

(2/4) We found that knockdown of CHD1 in a xenograft model of MYC-driven breast cancer suppresses tumor growth in vivo. In tissue culture models, knockdown of CHD1 suppresses cell proliferation and induces cell death, specifically when MYC is overexpressed.

CHD1 is a synthetic lethal vulnerability in MYC-driven breast cancer The MYC transcription factor is a key regulator of growth during development and a potent cancer driver when its expression is dysregulated. Strategies to inhibit MYC oncogenic activity would mark a s...

(1/4) New preprint from the lab!
The MYC transcription factor is a potent cancer driver when its expression is dysregulated, but efforts to target MYC directly have not been fruitful. We identify CHD1 as a synthetic lethal vulnerability in MYC-driven breast cancer. www.biorxiv.org/content/10.1...

Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development - Nature Communications Here they identify Tex10 as a critical regulator of male fertility and germ cell development. By fine-tuning Wnt signaling, Tex10 promotes spermatogenesis and PGC differentiation, offering potential t...

Also noted:
Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development. www.nature.com/articles/s41...

A single-cell time-lapse of mouse prenatal development from gastrula to birth - Nature Single-cell transcriptome profiling of mouse embryos and newborn pups is combined with previously published data to construct a tree of cell-type relationships tracing development from zygote to birth...

‪Discussed @mrsantos.bsky.social lit review: A single-cell time-lapse of mouse prenatal development from gastrula to birth.
www.nature.com/articles/s41...

🌞 Let's enjoy the summer time in Toronto! 🏖️