Zenlabpasteur.bsky.social

Translocation of the Notch3 Intracellular Domain (green) to the nucleus in adult neural stem cells (top), but retention at the membrane upon gamma-secretase inhibition (bottom).

New preprint out! Novel transgenic lines directly read out Notch3 signaling in situ, and reveal how adult neural stem cells coordinate quiescence and stemness by integrating spatiotemporal information from Delta and Jagged ligands. Read more: doi.org/10.1101/2025...

Engineer position, 12 months starting Oct. 1st, 2025, to study the role of NOTCH3 in human iPSC-derived neurogenesis models. Solid previous expertise required in cell culture, notably iPSCs, and organoid generation. Send CV, motivation letter and reference letter(s) to laure.bally-cuif@pasteur.fr

New call for research Group Leaders at Institut Pasteur Paris !

Non-apoptotic caspase events and Atf3 expression underlie direct neuronal differentiation of adult neural stem cells Highlighted Article: An inducible Cas3*/Cas7* sensor demonstrates that non-apoptotic caspase events occur in zebrafish neural stem cells. In cooperation with the stress-induced transcription factor At...

Just published in Development (@biologists.bsky.social):
doi.org/10.1242/dev....

On Mon 18/11, we held a mini symposium on the novel perspectives in human embryo research @institutpasteur. Lively discussions thanks to our prominent speakers/chair
Thanks to Nicolas Rivron; Alain Chédotal; Cécile Martinat; Ken McElreavey; Bernadette De Bakker and the chair Alfonso Martinez Arias

This also draws yet another parallel between physiological regulation stem cell pools and oncogenesis, which has been referred to as a process through which cells become “asocial” and cease to coordinate with their neighbors (18/18)

Although we were not able to identify what advantage this confers for NSC homeostasis, this non-canonical maintenance of Notch effectors illustrates different scales of quiescence regulation with some cells seemingly being able to listen less to their neighbors (17/18)

In vivo experiments confirmed that expression of nr2f1b in zebrafish NSCs is associated with a weaker response to Notch inhibition and functional experiments with morpholinos or electroporations of nr2f1b confirmed its ability to decrease sensitivity to Notch inhibition. (16/18)

Interestingly NR2F1 had previously been identified as a regulator of Notch signaling in the mouse inner ear (journals.biologists.com/dev/article/...), with downregulation of Notch effectors in NR2F1 knock-out mutants (15/18)

Using a gradient boosting method derived from SCENIC applied to both control and treated cells, we identified NR2F1/Coup-TF1 in sillico as a putative regulator enabling this resistance to Notch inhibition. (14/18)

Finally, we also identified that one cluster of cells barely responded to Notch inhibition, maintained expression of Notch effectors and did not upregulate genes associated with NSC activation. (13/18)

Although there are obvious differences between parenchymal astrocytes in mouse and astrocyte-like RGs in zebrafish, this suggests that comparative studies focusing on these cells might help better understand how to promote brain regeneration. (12/18)

The reported properties of the induced activation of these cells indeed shared similarities with that of astrocyte-like NSCs in the zebrafish pallium, such as participation in regeneration or reliance on Notch signaling (11/18)

Harmonizing the different reports of cell classification led us to consider that the cells that had been described as latent NSCs under different names in different publications were in fact likely the same population of parenchymal astrocytes close to the lateral ventricles. 10/18

Using the set of genes which we previously identified as allowing for distinction between murine RGL and astrocytes, we reclassified qNSC1 cells as astrocytes, in accordance with scRNAseq and in situ data from A Cebrian-Silla and methylome data from LPM Kremer. (9/18)

We found that the distinction between qNSC1 and qNSC2 had not been made in most cases even when the cells belonging to each group were present in the dataset. (8/18)

To get a clearer picture we re-analyzed scRNA-seq datasets encompassing the SVZ, generated by the labs of F Doetsch (@doetschlab.bsky.social), A Martin Villalba, J Frisen, S Linnarsson (@slinnarsson.bsky.social), J Biernaskie, N Rajewsky, F Miller, A Alvarez Buylla and O Raineteau. (7/18)

A similar phenomenon had been described in mouse astrocytes and putative subventricular zone (SVZ) radial glia-like (RGL) (called qNSC1) which respond to injury. (6/18)

In particular we found that one group of NSCs, recently described as being very similar to mouse parenchymal astrocytes, is efficiently recruited by Notch inhibition leading to the appearance of a cell state defined by co-expression of astrocytic and activating NSCs markers. (5/18)

With scRNAseq after 24hours of Notch inhibition we found that most cells had responded, but not in the same way. (4/18)

We attempted to push NSCs out of quiescence using Notch inhibition to see if previously identified clusters reacted differently to a pro-activation stimulus. (3/18)

Drawing from previous characterization of the heterogeneity of adult Neural Stem Cells (qNSCs) in the zebrafish pallium and the prediction that some of that heterogeneity comes from differences in quiescence depth (2/18)

New pre-print from the lab out on @biorxivpreprint (www.biorxiv.org/content/10.1...). 1/18