Swarnabh Bhattacharya

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Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells - Nature Cell Biology McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

How do #stemcells integrate information to coordinate fate decisions? Delighted to finally see our work showing how growth factors regulate the mechano-osmotic state of the #nucleus and #chromatin to control #pluripotency exit out! www.nature.com/articles/s41... see 🧵 👇

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Catch up on Development presents… webinar on gut development - the Node Our September webinar featured three early-career researchers working on gut development. Here, we share the talks from Surojit Sural (Columbia University) and Swarnabh Bhattacharya (Dana-Farber Cance...

Catch up on Development presents… webinar on gut development

Check out the talks of Surojit Sural @surojitsural.bsky.social & Swarnabh Bhattacharya @iamzico.bsky.social

Also, register for our upcoming #DevPres on 15 October: us02web.zoom.us/webinar/regi...

thenode.biologists.com/catch-up-on-...

Our next #DevPres webinar focusses on gut development with talks from Surojit Sural @surojitsural.bsky.social, Swarnabh Bhattacharya @iamzico.bsky.social and Brittany Edens, chaired by Alex Eve @amjeve.bsky.social.

📆 17 September, 15:00 BST (UTC+1)

Register here: us02web.zoom.us/webinar/regi...

Thanks to @rkzwick.bsky.social for writing this excellent preview and thoughtful discussion on our recent article @cp-cellstemcell.bsky.social (t.co/TkDxt1b3DH)

Honored to receive a Pilot & Feasibility grant (P30 DK034854) from the Harvard Digestive Disease Center to explore cellular plasticity and the epigenetic drivers of inflammatory bowel disease. Excited to uncover new insights into IBD pathogenesis!

To play Paneth or goblet: Shapeshifting secretory cells read the room The intestinal secretory lineage is thought to comprise four distinct cell types derived from one Atoh1+ progenitor, but the mechanisms that distinguish Paneth and goblet cells are unclear. Bhattachar...

I’m thrilled to have our work—“Intestinal secretory differentiation reflects niche-driven phenotypic plasticity of a common signal-responsive terminal cell” (dlvr.it/TK2Fzl) featured in the Preview of this issue of @cp-cellstemcell.bsky.social!

Glucose-6-phosphate-dehydrogenase on old peroxisomes maintains self-renewal of epithelial stem cells after asymmetric cell division - Nature Communications Peroxisomes are essential but their role in cell fate regulation remains understudied. Here, the authors reveal that young and old peroxisomes are not equally distributed in asymmetrically dividing st...

Happy to present Hien’s paper on age-selective apportioning of peroxisomes as a fate determinant in adult stem cells www.nature.com/articles/s41... @metastem.bsky.social @helsinki.fi @ki.se @helsinki-biotech.bsky.social out now in @natcomms.nature.com
A thread 🧵 1/9

Check out this exciting preprint from @aznarbenitahlab.bsky.social discovering a new mode of crosstalk between YAP and the circadian regulator BMAL1. Congrats @juliabonjoch.bsky.social and @guiomarsolanas.bsky.social for fantastic work and thank you for the fun collaboration!

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell Bhattacharya et al. delineate chromatin and mRNA dynamics of intestinal secretory differentiation. They demonstrate that goblet and Paneth cells are phenotypic variants of a facile signal-responsive ATOH1+ cell type and that goblet and Paneth cis-elements and the canonical genes they control interconvert upon modulation of Wnt and BMP signals.

Online Now! Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell #stemcells

I want to give a big shoutout to my mentor Ramesh Shivdasani, my fellow lab members, and all the fantastic collaborators. It was an excellent team effort.
Here is a link to the full text: authors.elsevier.com/c/1kusf6tu0C...
#PanethCell #GobletCell #Epigenetics #IntestinalBiology

A minority of enhancers are uniquely activated in Paneth cells under Wnt-favored conditions, shedding light on how epigenetic priming directs cell function along the crypt–villus axis.

Beyond phenotypic plasticity, our study maps cis-regulatory dynamics of intestinal secretory differentiation: Tuft and EE cells display thousands of unique enhancers, while many goblet and Paneth enhancers are shared with intestinal stem cells.

These insights redefine how we think about cell fate in the intestinal epithelium. Instead of being fixed identities, goblet and Paneth cells may be viewed as flexible, context-dependent states—a paradigm shift with potential implications for understanding intestinal diseases.

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A striking aspect of our findings is the reversible nature of this phenotypic switch. Even post-mitotic cells can rapidly convert their secretory identity in response to local niche signals—a process underpinned by dynamic chromatin changes.

Under forced Wnt and especially low BMP conditions, goblet cells gain Paneth features; conversely, BMP exposure potently suppresses Paneth markers and enhances goblet gene expression both in mouse and primary human 2D culture cells.

Experimentally, we demonstrated this plasticity by altering Wnt/BMP levels in vivo (e.g., via Apc deletion and RSPO modulation) and in organoid cultures.

Niche signals play a pivotal role! High Wnt and low BMP signaling, characteristic of the crypt base, push ATOH1+ cells to adopt a Paneth profile, while increased BMP (and lower Wnt) as cells move up the crypt drive a goblet cell phenotype.

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Our data show that both cell types originate from a common ATOH1+ secretory progenitor. Rather than being independently specified, goblet and Paneth cells share most mRNAs and many regulatory elements—only a few key antimicrobial genes differentiate them.

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Using lineage tracing with Atoh1Cre-ER mice, along with single-cell RNA and chromatin accessibility (snATAC-seq) analyses, we found an unexpectedly high overlap in the transcriptomes and epigenetic landscapes of goblet and Paneth cells.

The intestinal epithelium renews rapidly from stem cells, generating absorptive enterocytes and secretory cells. While enteroendocrine and tuft cells follow distinct trajectories, goblet and Paneth cells have long been thought of as separate terminal fates—until now.

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell Bhattacharya et al. delineate chromatin and mRNA dynamics of intestinal secretory differentiation. They demonstrate that goblet and Paneth cells are phenotypic variants of a facile signal-responsive A...

I am excited to share my latest Postdoctoral work @cp-cellstemcell.bsky.social @cellpress.bsky.social (dlvr.it/TK2Fzl), in which we reveal that goblet and Paneth cells aren’t fixed lineages but represent dynamic states influenced by local cues. Here's a walkthrough of what we found (🧵)....

Different fibroblast subtypes propel spatially defined ileal inflammation through TNFR1 signaling in murine ileitis @naturecomms.bsky.social
www.nature.com/articles/s41...

Multiple layers of γδ IEL dysregulation and loss of their immunosuppressive capacity occur before the onset of chronic ileitis
www.science.org/doi/10.1126/...
@nbgolovchenko.bsky.social @sciimmunology.bsky.social @edelblumlab.bsky.social

Vagal pathway activation links chronic stress to decline in intestinal stem cell function @cp-cellstemcell.bsky.social
www.cell.com/cell-stem-ce...

🔦Spotlight of Peter Dempsey, @brumbaugh-lab.bsky.social et al paper: Epigenetic fluidity meets phenotypic malleability in intestinal epithelial cells by @iamzico.bsky.social and Ramesh Shivdasani at @danafarber.bsky.social http://dlvr.it/TJfVRZ

It was fun to write this Spotlight article @cp-cellchembiol.bsky.social on the recent NCB paper (rdcu.be/eayN3) by @brumbaugh-lab.bsky.social & Dempsey labs, revealing how epigenetic fluidity drives phenotypic malleability in the intestinal epithelium. www.sciencedirect.com/science/arti...

Measuring and manipulating mechanical forces during development - Nature Cell Biology This Review discusses the recent advances in experimental approaches to interrogate the mechanical forces that mediate tissue deformations during development, highlighting the insights afforded at bot...

Happy to share our review on methodology for measuring and manipulating mechanical forces with specific focus on developmental biology! Congrats to authors @clemvilleneuve.bsky.social @mccreery.bsky.social and hats off to the community for developing awesome tools www.nature.com/articles/s41...