Lucas Cheadle

Shout out to wonderful collaborator @briankalishMD and funding from @hhmi_science @CSHL @NIMHgov @McKnightFdn Rita Allen Foundation

This study underscores the importance of studying autism not just from a neurological perspective but in the context of immunology as well.

Follow up experiments directly testing this hypothesis and extending our findings to human biology are underway.

We hypothesize that male embryos express unique factors, i.e. antigens that are non-self to the female dam, that, when combined with a loss of placental immunosuppression due to maternal infection, derails fetal development in males.

We hypothesize that male embryos express unique factors, i.e. antigens that are non-self to the female dam, that, when combined with a loss of placental immunosuppression due to maternal infection, derails fetal development in males.

What we think is most exciting: out of hundreds of embryos analyzed, only males exhibited these phenotypes. Female embryos and placentas were protected in every single case.

Innate immune cells and cytokines accumulate within the amniotic fluid, with one of these cytokines, IL6, being necessary for the deficits to emerge.

The placentas of affected male embryos exhibit structural deterioration near the region where maternal and fetal compartments meet.

Concurrently, placental cells called spongiotrophoblasts decrease ECM and hormone expression following MIA, leading to a loss of immunosuppression at the maternal-fetal interface.

These abnormalities coincide with the induction of a pro-inflammatory placental microenvironment, with both maternally and fatally derived immune cells mounting inflammatory responses.

Using a mouse model, we find that only 24 hours of maternal immune activation (MIA) during pregnancy leads to robust developmental deficits in 30% of embryos.

Two major gaps in knowledge: 1. What inflammatory triggers derail fetal brain development? 2. Why are some individuals susceptible to these triggers while others are not?

While genetic factors contribute to autism, environmental factors such as prenatal inflammation can also play a key role. For example, maternal infections during pregnancy increase autism risk in the offspring.

Excited to share new work from the Cheadle Lab investigating the inflammatory basis of autism spectrum disorder (tweetorial below)

biorxiv.org/content/10.648…

So glad we had the chance to contribute to this beautiful study on neuronal function in breast cancer. Fantastic collaboration w @jborniger.bsky.social and @corina-amor.bsky.social

Thank you!

Figure 1 - Experimental design and introduction to the single-nucleus RNA sequencing dataset. (A) Schematic illustrating the late dark-rearing (LDR) paradigm and the workflow of the single-nucleus RNA sequencing (snRNAseq) experiments. (B) Quantification of Fos mRNA expression in sensory deprived (LDR) mice and in mice acutely exposed to light for between 15 min and 2 h, with stimulation timepoints labeled as follows: LDR15m (15 min of light), LDR30m (30 min), LDR1h (1 h) and LDR2h (2 h). Fos expression assessed by qPCR and normalized to Gapdh. Values plotted are additionally normalized to the LDR condition. (C) qPCR quantification of Jun mRNA expression (normalized to Gapdh) in V1 across all timepoints. Data obtained by qPCR and values plotted are normalized to LDR. In B and C, data are mean±s.e.m. n=3 mice per condition. One-way ANOVA followed by Tukey's post hoc test: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. (D) Example confocal images of V1 in sections from a sensory deprived mouse (LDR) and a mouse re-exposed to light for 30 min (LDR30m). Fos mRNA (red), Jun mRNA (green) and DAPI (blue). Scale bar: 44 µm. (E) UMAP plot illustrating the 118,529 nuclei in the dataset categorized by general cell class: excitatory neurons (blue), inhibitory neurons (pink) and glia (green). (F) UMAP plot with all 16 clusters colored and labeled by cell type.

A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex

Read this this #LifelongDevSI #OA Techniques and Resources Article by Andre M. Xavier, Qianyu Lin, Chris J. Kang, Lucas Cheadle (@cheadlelab.bsky.social)

doi.org/10.1242/dev....

Thrilled to welcome the new FHS cohort… including these newly selected McKnight Scholars!

That’s my plan!

Wish I had known you were around!

Love this

Hosting Dr. Kaf Dzirasa @hhmi.org for a seminar at CSHL and getting to spend time w/fellow FHS @ishmailsaboor.bsky.social in the process has made this week a highlight of my year. Feeling seriously inspired today.

A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex Summary: Single-cell RNA sequencing of developing mouse visual cortex uncovers cell type-specific gene programs induced by sensory experience. All cell types mounted transcriptional responses to the e...

journals.biologists.com/dev/article/...

New work from the lab characterizing sensory-dependent transcriptomes in mouse V1 across neuronal and glial cell types. Some fun nuggets in here, and all data publicly available for download and re-analysis. Happy gene hunting!

Congrats!

Awesome to see this!

I’m curious whether the men were mentored to say “no” while the women were mentored to say “yes”. My mentors have always taught me to embrace saying “no” but maybe this advice differs by gender?

Delighted to share the published version of this work from brilliant #CancerNeuroscience post-doc Tara Barron detailing GABAergic neuron-to-glioma synapses in #DIPG/#DMG. 🧵
Open access link:
www.nature.com/articles/s41...

Dear friends and colleagues: nice to see you here where the skies are bluer. Follow me for updates on our research into neuro-immune interactions in brain development, function, and disease. @cshlnews.bsky.social @hhmi.bsky.social