Pierre Mattar
pierre-mattar.bsky.social
Pierre Mattar
@pierre-mattar.bsky.social
Momentous day yesterday as Ivana Herrera successfully defended her doctoral thesis. Huge congratulations to her (seated center). Very proud of her!
February 22, 2025 at 8:46 PM
February 9, 2025 at 3:37 PM
Jack this morning: It warm!!
February 5, 2025 at 2:48 PM
Next, we used single-cell RNA-seq, cut&run-seq, and ATAC-seq to figure out how Chd4 regulated the epigenome and transcriptome. Basically, we think that chromatin remodelling is important for progenitors to be able to change themselves. Without remodelling, they get stuck.
January 18, 2025 at 1:44 PM
At late stages, there was a clear shift in the temporal state of the progenitors in the mutant. Many were still dividing, when they would have normally been exhausted (mainly from making lots of rod photoreceptors).
January 18, 2025 at 1:44 PM
...and when we mutated Chd4, the phenotype looked right. We ended up with pretty dramatic distortions in the cell-type composition of the retina. A big expansion in early-born retinal ganglion cells. A contraction in late-born rod photoreceptors. But also ~double the latest-born Müller glia.
January 18, 2025 at 1:44 PM
There are a few theories about how neural progenitors can do this. Probably the main theory is that dynamically expressed transcription factors do it. This mechanism was first discovered in Drosophila neuroblasts, which also generate neuron subtypes in chronological sequences.
January 18, 2025 at 1:44 PM
The consensus in the field is that the progenitor changes itself over time. That allows it to change what it makes. By changing itself, it can generate sequences of different kinds of neurons. And at the end, the progenitor will finally change itself into a Müller glia.
January 18, 2025 at 1:44 PM
Moreover, gene expression was misregulated. In particular, we see a global effect on the expression of risk genes associated with neurodevelopmental disorders - particularly in neurons. Eg., here are SFARI ASD risk genes. Green arrow: upper layer neurons
February 14, 2024 at 7:23 PM
Athough ADNP and CHD4 proteins are expressed ubiquitously, we found that ChAHP was required in a context-dependent manner. Knockouts exhibited defects in the proliferation of apical progenitors specifically during the developmental window for upper-layer neuron production.
February 14, 2024 at 7:23 PM
In the paper, we got around this by generating conditional mutants for Adnp and Chd4. We generated a new floxed allele in order to do this with Adnp. We characterized neocortical development and ChAHP functions using scRNA-seq, cut&run-seq, and histological approaches.
February 14, 2024 at 7:22 PM
New preprint from the lab. This one is (again) about about modelling neurodevelopmental disorders. Here, we focus on the link between chromatin remodellers (ADNP and CHD4) and cortical development. #NDDs and #cortical development. www.biorxiv.org/content/10.1...
February 14, 2024 at 7:20 PM
February 14, 2024 at 2:03 AM
Glad to see snowmen finally being emotionally honest with themselves.
January 27, 2024 at 11:15 PM
Compound eye selfie
December 24, 2023 at 9:55 PM
Update:
December 9, 2023 at 5:48 PM
Today’s vibe
December 9, 2023 at 4:59 PM
However, we showed previously that lamin A - an alternative splice variant that has a longer C-terminus - is sufficient.
October 27, 2023 at 4:47 AM
After all, rod photoreceptors have a highly unusual nuclear architecture. While most cells localize heterochromatin at the nuclear lamina, mouse rods are 'inverted'. Heterochromatin (bright cyan) is centralized, and euchromatin (marked by Crx - red) is present at the lamina.
October 27, 2023 at 4:46 AM
Perhaps these differences shouldn't have surprised us, but I think it is really interesting how discordant the results are.
October 27, 2023 at 4:35 AM