System-level regulation of hierarchical transitions in a tumour lineage
The fundamental principles defining how cell state transitions are regulated along a tumour lineage to determine its cellular composition remain unclear. Here, we investigate how such transitions are controlled in a reductionist hierarchical brain tumour model. Quantitative analysis of 3D transition maps revealed that the differentiation of cancer stem cells (CSCs) into transit amplifying progenitors (TAPs) depends on the identity of their immediate neighbours. This is embodied in a transition rule that quantitatively predicts the probability to differentiate as a function of the proportion of TAP neighbours. Integrated into 3D simulations of tumour growth, this rule spontaneously recapitulates spatial segregation of CSCs in clusters and their stable proportion. We further show in vivo that CSC clustering protects the CSC pool from depletion driven by TAPs. We identify an EGFR-mediated relay mechanism that propagates the CSC-to-TAP transition across CSC clusters. In CSCs, the LRIG1-like EGFR inhibitor Kekkon1 dampens this propagation, ensuring continuous replenishment of the CSC pool. Collectively, these findings show how local fate regulation drives emergent segregation which in turn constrains CSC differentiation dynamics. This provides a conceptual framework to understand and exploit the tumour’s intrinsic differentiation potential by manipulating the determinants of its system-level features. ### Competing Interest Statement The authors have declared no competing interest. Turing Centre for Living Systems (CENTURI) La Ligue Contre le Cancer, https://ror.org/00rkrv905, Equipe Labellisée LIGUE 2025 Fondation pour la Recherche Médicale, ANR-24-EXCI-0001, ANR-24-EXCI-0002, ANR-24-EXCI-0003, ANR-24-EXCI-0004, ANR-24-EXCI-0005 Agence Nationale de la Recherche under the France 2030 program, ANR-24-EXCI-0001, ANR-24-EXCI-0002, ANR-24-EXCI-0003, ANR-24-EXCI-0004, ANR-24-EXCI-0005 Centre South-ROCK, INCa-Cancer_18695
Tumours aren’t just a messy mix of cells—they’re highly organised and hierarchical societies!
Just like in all societies, small chats between individuals can drive collective emergent behaviours - we reveal how these sustain tumour growth and cellular heterogeneity. 🧵👇
28.01.2026 21:53 — 👍 14 🔁 6 💬 2 📌 0
Using quantitative 3D mapping of cell state and cell neighbourhood in whole tumours, we show that cancer stem cells probability to differentiate is a quantifiable function of their neighbourhood, and that the differentiation signal is emitted by the surrounding differentiated cells.
28.01.2026 13:59 — 👍 1 🔁 0 💬 0 📌 0
Super happy to share the exciting work of Emma Legait, showing how neighbourhood composition determines cancer stem cell fate in hierarchical tumours. A great and long-standing collaboration with @cedricmaurange.bsky.social
www.biorxiv.org/content/10.6...
28.01.2026 13:54 — 👍 11 🔁 4 💬 1 📌 0
Big welcome to our new PhD students @anitabichisecchi.bsky.social and @petramikec.bsky.social !! 🙌🏼💥🥚📸
01.10.2025 14:50 — 👍 13 🔁 3 💬 1 📌 1
Very happy to introduce jsPCA, a fast and interpretable computational framework for spatial transcriptomics that simultaneously identifies spatial domains and variable genes across multi-slice and multi-sample data.
19.09.2025 06:49 — 👍 17 🔁 8 💬 2 📌 0
Thank you Adrien :)
28.08.2025 15:04 — 👍 1 🔁 0 💬 0 📌 0
Mechanosensation and fast reorientation of ciliary structures: Marvin's work on the surprising locomotion capabilities of Trichoplax, an animal without neurons!
www.biorxiv.org/content/10.1...
27.08.2025 10:50 — 👍 75 🔁 25 💬 1 📌 1
Sham Tlili, winner of the CNRS 2025 bronze medal - IBDM | Institut de Biologie du Développement de Marseille
A distinction that rewards a promising and already fruitful scientific career.
🥇Sham Tlili has been awarded the CNRS 2025 Bronze Medal! She studies how physical forces shape living tissues by using mouse stem cell models known as gastruloids. A unique blend of physics & biology.
🔗 Read more: www.ibdm.univ-amu.fr/sham-tlili-w...
27.06.2025 09:00 — 👍 45 🔁 14 💬 2 📌 0
Déployer ses ailes : la première étape cruciale de l’insecte adulte 🪰🦋🐞 Un article grand public avec @simonhadjaje.bsky.social et édité par Elsa Couderc
06.05.2025 17:37 — 👍 9 🔁 4 💬 0 📌 0
🚨 PhD Opportunity! 🚨
Passionate about ovarian biology? This cutting-edge PhD project combines live-cell microscopy & biophysical modelling to explore the dynamic ovary! 🧬🔬
I'm happy to chat more—DM or email me to set up a Zoom call 📩 And please share! 🙌🏼
christopher.thomas@univ-amu.fr
19.03.2025 07:07 — 👍 30 🔁 18 💬 1 📌 0
How insects unfold their wings !
rdcu.be/d28vT
13.12.2024 14:30 — 👍 30 🔁 8 💬 0 📌 0
PostDoc in the Ladoux-Mège lab at Institute Jacques Monod in Paris. Interested in mechanobiology, epithelial dynamics, cell competition and differentiation
Asst. Prof. in Physics
LSA Collegiate fellow
University of Michigan
Previously JF at Harvard & PhD at SU
he/him
https://sites.lsa.umich.edu/shankar-lab/
How function emerges collectively in soft, active, living matter? | Physics, maths, & biology
MPI-CBG, Paul Langerhans Institute (PLID) -Developmental and stem cell biologist- Physics of Life
#Mechanics of #zebrafish, #ascidian, and #drosophila #development @Institute of Science and Technology Austria (ISTA)
https://heisenberglab.pages.ist.ac.at
Scientist, teacher, mentor, mom, yogini, jogger, reader...we study how cells move, build, maintain, and repair tissues. Our fruit fly work has unexpectedly led us to an improved cancer immunotherapy we call RaceCAR-M.
The aim of our research group is to elucidate the mechanism that underlies the development of the Neural Crest, from induction to migration and differentiation.
https://t.co/LSkrQBj6gm
I sail the vast sea of gastruloids, guided by the flow of embryonic tissue development — just after gastrulation!
Home port: IBDM, Marseille
🔬 Junior Group Leader in Münster, Germany.
🌐 Lab Website: https://www.bischofflab.com/
🌀 Morphogenesis, collective cell migration, and chiral organ development in #Drosophila.
🐍 Animal photos: 📷 instagram.com/maikscritters
Our lab unravels the mechanobiology and cellbiology of immune cells, their migration & cytoskeleton, their organelles, and their cell-matrix interplay using #imaging, #screening, and #bioengineering
@bmc-lmu.bsky.social
www.renkawitz-lab.com
PhD student at @ibdm.bsky.social, exploring how ovarian follicle dominance is acquired. Previously at @crick.ac.uk working on epithelial stem cells applications for regenerative medicine
CENTURI PhD at IBDM | Thomas lab 🫧🔬
Virginie Hamel & Paul Guichard Lab at University of Geneva
#cryoEM/ET❄️ and #UExM ⚗️ #ExpansionMicroscopy #TeamTomo
Genève, Suisse 🇨🇭
https://mocel.unige.ch/research-groups/guichard-hamel/overv
Doing #EpithelialMechanics! with chick embryo 🐣
Convenor @epimechfc.bsky.social // Postdoc @NerurkarLab at Columbia // PhD @xaviertrepat.bsky.social lab at IBEC Barcelona
nchahare.github.io
Manning Research Group at Syracuse University: theory and computation focused on cells, grains, tissues, glasses, and other out-of-equilibrium disordered matter
The Ramsey philosophy of biology lab at KU Leuven, Belgium.
https://www.theramseylab.org • #HPbio #philsci #philsky #evosky #paleosky #cogsci
Postdoctoral researcher at Physics of Life, TU Dresden. I study early morphogenesis in a zebrafish model.
Assistant Professor Sorbonne Université - Developmental Biologist 🧫 Morphogenesis enthusiast. Interested in Open & Sustainable Science 🌈
Cell and Developmental Biologist @ St. Jude Children's Research Hospital - 🦔 signaling in 🧠🫀&🫁 - science 🧪, academia, DevBio research, mentoring, scicomm, 🔬, birds 🪶, hikes - fueled by ☕ & 🧘🏼♀️ - Y’all means all - Views my own and not SJCRH's
Evolution of neurons and nervous systems / choanoflagellates / sponges / ctenophores. Deputy Director & Group leader at the Michael Sars Centre, University of Bergen. Webpage: https://www.uib.no/en/michaelsarscentre/114773/burkhardt-group
