Bewick Lab

In mice. "Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance"
www.sciencedirect.com/science/arti...

Measurement of Real-Time Serotonin Dynamics from Human-Derived Gut Organoids The importance of the gut in regulating the brain–body immune axis is becoming increasingly evident. Interestingly, the brain and gut share many common signaling molecules, with serotonin being one of the most notable. In fact, the gut is the primary source of serotonin in the body. However, studying serotonin dynamics in a human-specific context remains a challenge. Human stem cell-derived models provide a promising avenue for studying signal transmission in well-controlled, in vitro environments. In this study, we report the first fast-scan cyclic voltammetry (FSCV) measurements of serotonin signaling in a newly developed enterochromaffin cell (ECC)-enriched gut organoid model. First, we characterize the stem cell-derived gut organoids and confirm they are enriched with ECCs, the key cell type responsible for producing and releasing serotonin in the gut. We then optimize an in vitro buffer that maintains cell viability while supporting FSCV measurements. Using this system, we detect spontaneous release events, which increase in frequency and amplitude following stimulation with forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX). Finally, we confirm the identity of the signal as serotonin using a selective serotonin reuptake inhibitor (SSRI), which significantly delayed the reuptake profile. Our study introduces the first real-time measurement of serotonin signaling in a human-derived gut model. We believe this system will be essential for future research on serotonin’s role in the gut and for potential novel drug target identification.

Fab collaboration with @HashemiLab! where we optimized their voltammetry technique to measure realtime secretion of #serotonin from human #gut #organoids. Led by 2 awesome ECRs @yuxian_lei and Bettina Bohl.
@kingscollegelondon.bsky.social
@kingshealth.bsky.social

pubs.acs.org/doi/10.1021/...

A privilege to attend the launch of the @thelancet.bsky.social commission on clinical obesity with @kingshealth.bsky.social Great discussions on how a new definition of clinical obesity impacts policy, prevalence calcs, management, treatment, stigma and research in the field.

Gcg+ cNTS neurons monitor intestinal nutrients, cumulative ingested calories and have long-term effects on satiation.

Th+ cNTS neurons encode esophageal distension and gulp size via vagal afferent inputs, providing quick feedback regulation of ingestion speed.

www.nature.com/articles/s41...

@lifemetabolism.bsky.social is now indexed on PMC. Come on down and check out our great content. Please share and repost.

Glp1r-Lepr coexpressing neurons modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist Orthogonal murine models demonstrate the bioactivity and neuronal targets of a GLP-1/leptin coagonist in relation to food intake and body weight.

Latest from our group in collaboration with Lotte Bjerre Knudsen and other Novo scientists. They developed a GLP-1/Leptin co-agonist that we put through its paces in a number of mouse models to prove that both parts of the molecule matter. More options on the table!
www.science.org/doi/10.1126/...

The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice The functional role of peripheral GIPR action in weight loss is yet to be fully defined in a preclinical setting. Here, Yu et al. propose a mechanism whereby inducible activation of GIPR in adipocytes promotes energy wasting through futile calcium cycling, triggering profound weight loss in the obese state.

The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice 🧪

www.cell.com/cell-metabol...

Prepint has been out for a bit, but now you can read the skeetorial as well.

See how you can map the impact of disease across the whole body.

Glp1r-Lepr coexpressing neurons modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist Orthogonal murine models demonstrate the bioactivity and neuronal targets of a GLP-1/leptin coagonist in relation to food intake and body weight.

LepR positive for Glp1r neurons represent targets for a GLP-1R/LepR dual agonist that potently reduces food intake and body weight.

www.science.org/doi/10.1126/...

U.K. to restrict Eli Lilly’s obesity drug to patients with greatest need The U.K. will soon offer Eli Lilly's Mounjaro for people with obesity — but only to a small share of those medically eligible, and alongside a specialized diet.

Sure, but how are those with greatest need going to be identified. Difficult choices to be made.
#obesity #GLP-1

www.statnews.com/2024/12/04/o...

Regenerative drugs may be targeting cycling alpha cells in human islets.

www.cell.com/cell-reports...

Fantastic McDowell lecture by the awesome Andy Pepper @PepperLab_UofA for @KclPhysiology. Great to chat about all things science, fishing and life in general! @AlbertaDiabetes. #diabetes #islets #T1D

This paper is important. It provides a really strong case for working as hard as possible to include samples from those centres that serve the traditionally underrepresented patient groups in research. If we want treatments to work on everyone, we need to ensure research includes everyone.

High content of nuclei-free low-quality cells in reference single-cell atlases: a call for more stringent quality control using nuclear fraction - BMC Genomics The advent of droplet-based single-cell RNA-sequencing (scRNA-seq) has dramatically increased data throughput, enabling the release of a diverse array of tissue cell atlases to the public. However, we...

Not checking nuclear markers like MALAT1 or intronic reads in your scRNA-seq data?🚨
We show their power to flag low-quality cells—even in top public datasets. It’s time to prioritize better QC for cleaner, more reliable genomics research!
Read more: bmcgenomics.biomedcentral.com/articles/10....
1/8

Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy - Nature Communications Methods to culture intestinal stem cells (ISCs) are often limited by undefined culture conditions arising from the use of basement membrane extracts or feeder cell layers. Here, the authors propose a ...

XF-DISC is highly promising for the development of regenerative ISC therapy for human intestinal diseases. #organoid
www.nature.com/articles/s41...

Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages Identification of an LGR5 as a marker for a tripotent stem/progenitor cell of the human fetal pancreas. Organoids derived from single LGR5+ cells are capable of long-term expansion in vitro and genera...

Human fetal pancreatic organoids generate functional acinar and endocrine cell lineages upon differentiation

LGR5 marks tripotent stem cells, precursors to all exocrine and endocrine lineages

www.cell.com/cell/fulltex...

Parallel gut-to-brain pathways orchestrate feeding behaviors - Nature Neuroscience This study identifies parallel gut–brain pathways that fine-tune feeding. Distinct brainstem neurons and visceral afferents either sense esophageal stretch to regulate eating speed or detect gut nutri...

Gcg+ cNTS neurons monitor intestinal nutrients and cumulative ingested calories and have long-term effects on food satiation and preference.
www.nature.com/articles/s41...

Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety Nature Metabolism - Combining rabies-based connectomics with single-nucleus transcriptomics, the authors identify a neural circuit through which GLP-1 receptor agonists suppress appetite in mice.

New work stemming from an amazing collaboration with @addisonwebster0 and @AUGCsoup using a combination of rabies mapping and single cell sequencing to identify a GLP1R-expressing local input to AgRP cells that curbs appetite rdcu.be/d2gB5

Reconstitution of Human Brain Cell Diversity in Organoids via Four Protocols Human brain organoids are powerful in vitro models for brain development and disease. However, their variability can complicate use in biomedical research and drug discovery. Both the specific protoco...

Must-read for 🧠 #organoid researchers: In a new preprint, the @knoblich-lab.bsky.social presents 4 organoid protocols that recreate the vast majority of cell types in the developing human brain. The data is freely available as a new #neuroscience reference.
www.biorxiv.org/content/10.1...

We know everything about IL-33 already, right?

No! In fact we know very little about IL-33 in the colonic epithelium

Our recent paper finds IL-33 is highly enriched in colonic stem cells suggesting an immunoregulatory role for this niche in injury🧵

www.mucosalimmunology.org/article/S193...

Hello could you add me gut #organoids #obesity #diabetes

@neuroendo.bsky.social can you add me to this great list?

Mature tuft cell phenotypes are sequentially expressed along the intestinal crypt-villus axis following cytokine-induced tuft cell hyperplasia Intestinal tuft cells are epithelial sentinels that trigger host defense upon detection of parasite-derived compounds. While representing interesting targets for immunomodulatory therapies in inflamma...

New work on #tuft cells, rare guardians of our #gut against invaders. How they work is not known. We show that intestinal tuft types 1&2 are sequentially expressed phenotypes during differentiation. And…we can now generate mature immune-related tuft-2’s in #organoids for more 🔬🧫🧬🔥
shorturl.at/EImjA

PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we ...

PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance | Science www.science.org/doi/10.1126/...

A panoramic view of cell population dynamics in mammalian aging To elucidate aging-associated cellular population dynamics, we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissues across different life stages, se...

Excited to share our work @science.org. led by our incredible @tommyz626.bsky.social at @rockefelleruniv.bsky.social! By profiling 21 million single cells across life stages, we reveal aging as distinct, development-like transitions, with dramatic cell population changes in specific time windows!

Microfluidic Organoids-on-a-chip: The future of human models

A very nice update on Done (& To-Do)
Brain
Heart
GI tract
Liver
Pancreas
Tumor

Explicit technical details

Flavio Rizzolio lab Semin Cell Dev Biol 2023
www.sciencedirect.com/science/arti...

Interoception and gut–brain communication The brain senses changes to the internal state of the body, eliciting responses that maintain homeostasis. Alhadeff and Yapici provide an overview of this process, termed interoception, with a particu...

Current Biology

Interoception and gut–brain communication
www.cell.com/current-biol...

Soil microbiomes show consistent and predictable responses to extreme events - Nature Soils from 30 grasslands across Europe were subjected to 4 contrasting extreme climatic events under drought, flood, freezing and heat conditions, with the results suggesting that soil microbiomes fro...

Science takes time - a lot of time. Time that is more and more difficult to make available because of increased workloads. Time that exceeds the temporary contracts of postdocs and PhDs.

I'll illustrate this using our paper published in Nature yesterday. 🧵 (1/x)
www.nature.com/articles/s41...

World map displaying the number of people with (A) diabetes and (B) untreated diabetes in 2022. Copyright: 2024 The Author(s). Published by Elsevier Ltd. CC BY 4.0.

Over 800 million adults are now living with #diabetes worldwide with more than half not receiving treatment, global analysis suggests.

Explore the findings ▶️ bit.ly/3Be89wl

Lipid droplet protein Perilipin 2 is critical for the regulation of insulin secretion through beta cell lipophagy and glucagon expression in pancreatic islets

https://www.biorxiv.org/content/10.1101/2024.11.17.624030v1