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SinghLab@SNIoE

@singhlab.bsky.social

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SinghLab@SNIoE @singhlab.bsky.social · Jun 6

🚨 Just out in Nature Communications:
Cholangiocytes contribute to hepatocyte regeneration after partial #liver #injury during growth in #zebrafish
We challenge old assumptions on liver regeneration!
🔗 nature.com/articles/s41...
🧵(1/8)

Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish - Nature Communications

During partial liver injury in growing zebrafish, cholangiocytes regenerate hepatocytes through transdifferentiation, revealing a stage-specific regeneration mechanism regulated by mTORC1 signaling.

nature.com

3 8 20

SinghLab@SNIoE @singhlab.bsky.social · Jul 31

As part of the Faculty Development Program at Shiv Nadar University , received these 10 commandments for faculty. This is the best advice I have seen, and certainly hits the nail on the head. Especially about focusing and getting the first study out early on.

SinghLab@SNIoE @singhlab.bsky.social · Jun 15

Thank you!

SinghLab@SNIoE @singhlab.bsky.social · Jun 6

Thank you!

SinghLab@SNIoE @singhlab.bsky.social · Jun 6

If you’re interested in liver regeneration, cholangiocyte biology, or cell fate plasticity, we’d love to hear your thoughts!

#LiverRegeneration #Zebrafish #RegenerativeBiology #CellPlasticity
(8/8)

SinghLab@SNIoE @singhlab.bsky.social · Jun 6

🙏 Funded by FNRS and DBTIndia, whose support was essential.
🐟 This study also highlights the power of #zebrafish as a model for dynamic cell plasticity and #regeneration.
🔗 Full paper: nature.com/articles/s41...
🔗 Lab: sumeetpalsingh.github.io
(7/8)

SinghLab@IRIBHM – Regenerative Biology

Injury and Stress Response

sumeetpalsingh.github.io

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SinghLab@SNIoE @singhlab.bsky.social · Jun 6

Huge thanks to our team:
👏 Lead author Sema Elif Eski

👏 Co-authors @jiaruimi.bsky.social Macarena Pozo Morales, Garnik Hovhannisyan
👏 Collaborators @o-andersson-lab.bsky.social Esteban Gurzov, Rita Manco, Federico Marini

(6/8)

SinghLab@SNIoE @singhlab.bsky.social · Jun 6

This reveals that cholangiocyte plasticity is not just a backup plan, but an active, physiological response during liver growth and moderate injury.

A new paradigm: transdifferentiation can occur without senescence, fibrosis, or chronic damage.
(5/8)

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SinghLab@SNIoE @singhlab.bsky.social · Jun 6

Surprisingly, de novo hepatocytes emerged even when spared ones were present—a key deviation from the idea that cholangiocytes only activate after massive hepatocyte loss.

We confirmed this with a 17% partial hepatectomy model. ✂️🐟
(4/8)

SinghLab@SNIoE @singhlab.bsky.social · Jun 6

Enter CellCousin: a new zebrafish tool we designed to trace liver regeneration.

🟢 Spared hepatocytes
🔴 Ablated hepatocytes
🔵 De novo hepatocytes (not hepatocytes before injury)
This lets us precisely map where new hepatocytes come from after injury.
(3/8)

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SinghLab@SNIoE @singhlab.bsky.social · Jun 6

The liver can regenerate itself—a fact known since the myth of Prometheus.
But when hepatocytes are damaged, can cholangiocytes step in to rebuild the liver even if some hepatocytes remain?
We built a new zebrafish model to test it.
(2/8)

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SinghLab@SNIoE @singhlab.bsky.social · Jun 6

Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish - Nature Communications

During partial liver injury in growing zebrafish, cholangiocytes regenerate hepatocytes through transdifferentiation, revealing a stage-specific regeneration mechanism regulated by mTORC1 signaling.

nature.com

3 8 20

Reposted by SinghLab@SNIoE

Filipa Simões @simoesfilipa.bsky.social · May 16

🫀Job alert 🧬 come and be our colleague! Join a BBSRC-funded consortium aiming to understand how the human heart develops - you will be contributing multimodal single cell & spatial transcriptomics data using zebrafish and human cardiac organoids as models. Learn more: www.heartdevelopment.org (1/4)

CellTalk HHD | Human Heart Development Research

CellTalk-Human Heart Development is a BBSRC funded consortium established to find out more about how cells come together to build the heart as it grows inside the womb.

www.heartdevelopment.org

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SinghLab@SNIoE @singhlab.bsky.social · Jun 2

Pleased to have contributed commentary to this recent article by Maria Bolevich for Interesting Engineering, which explores the science of tissue #regeneration and its potential applications in medicine.
Read the full article here: interestingengineering.com/health/body-...

Why the body's natural regeneration isn't enough to stop chronic disease

From skin renewal to liver repair, the body is rebuilding itself. Scientists are now uncovering why some organs heal and others don’t.

interestingengineering.com

SinghLab@SNIoE @singhlab.bsky.social · May 28

Huge thanks to the team and funding support FNRS, DBTIndia that made this happen 🙌
We hope CellCousin2 helps others studying regeneration, cell fate, and tissue repair.
All plasmids are available on @addgene.bsky.social

SinghLab@SNIoE @singhlab.bsky.social · May 28

How does DDCreER work?
We fused CreER to a destabilizing domain (DD) that is degraded unless stabilized by TMP.
💊 TMP = protein stabilization
🟣 4-OHT = nuclear translocation
Only when both are present does recombination occur—ensuring tight temporal control.

SinghLab@SNIoE @singhlab.bsky.social · May 28

What’s new in CellCousin2?
✅ DDCreER: chemically inducible Cre with low leakiness
✅ NTR2.0: ablation with 10× less metronidazole
✅ Cleaner, more precise regeneration readouts
The system is modular and adaptable to other tissues or models.

SinghLab@SNIoE @singhlab.bsky.social · May 28

What is CellCousin?
It uses stochastic recombination and NTR-based ablation to remove only a subset of hepatocytes.
🟢 Spared cells
🔵 New (De novo) hepatocytes
This allows direct comparison of lineage contributions during liver repair.

SinghLab@SNIoE @singhlab.bsky.social · May 28

We just posted our new preprint, spearheaded by Garnik Hovhannisyan in collaboration with Esteban Gurzov Lab! biorxiv.org/content/10.1... #zebrafish #liverregeneration #DevBio #LineageTracing

CellCousin2: An Optimized System for Partial Ablation and Tracing of Regenerative Lineages

Regeneration can rely on multiple cellular sources, including stem cells, self-duplicating cells, and transdifferentiating cells. A central question in regenerative biology is how these distinct linea...

biorxiv.org

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SinghLab@SNIoE @singhlab.bsky.social · May 26

Fantastic! Is it available from Etsy or another vendor?

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SinghLab@SNIoE @singhlab.bsky.social · May 21

Thank you Jiarui!

SinghLab@SNIoE @singhlab.bsky.social · May 16

Stunning 3D fluorescent images of the human #tooth and the first cellular/molecular map of tooth #decay! Hoang Thai Ha from Nicolas Baeyens Lab nails it with tissue clearing + imaging.
www.biorxiv.org/content/10.1...

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Reposted by SinghLab@SNIoE

Carol Yang @yhcarolyang.bsky.social · May 14

Interested in understanding how neural-pancreas interplay contributes to blood sugar control? We have an exciting PhD project to study galanin regulation of pancreatic #islet hormone secretion in live #zebrafish

www.exeter.ac.uk/research/ins...

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SinghLab@SNIoE @singhlab.bsky.social · May 14

Liver regeneration after killing part of the liver! In this image, the same liver from same #zebrafish is imaged before (left) and after (right) regeneration. The newly born liver cells are in blue.

Project led by @selifeski.bsky.social

SinghLab@SNIoE @singhlab.bsky.social · May 3

We celebrated a big milestone in our lab: our first #Undergrad intern presented her work at lab meeting! She helped develop two new #liver #injury models, and is on her way to becoming a fantastic scientist. Thanks to PhD student Garnik for mentoring her so well! 👏🧪 #TeamScience

SinghLab@SNIoE @singhlab.bsky.social · Apr 16

Amazing!