Berend Snijder’s Post

We are thrilled to share the results of our collaboration with ETH Zürich. Scientists from Berend Snijder's Lab at ETH Zurich discovered two functionally distinct populations of T cells many years ago. To help identify characteristics of these distinct populations, the researchers developed a platform that automatically analyses microscopy images of immune cells. They then presented this platform with thousands of T cells from 24 healthy volunteers who donated their blood to BLUTSPENDE SRK Zürich. We meticulously processed these cells to support the groundbreaking research at ETH Zurich. This new insight into the cellular architecture of T cells holds significant promise for advancing cancer therapies. ➡️ Read the research article: https://lnkd.in/ggKNxQnw We are always happy to contribute to and support research! 🚀 #tcells #pharmacoscopy #immunology #research #innovation

Breakthrough Discovery: Undisturbed Image Sorting Reveals How T Cells Decide Fate in Viral Infections This exciting paper revealed how naïve T cells decide to become effector or memory T cells during viral infections, crucial for long-term immunity. Using self-supervised deep learning for image processing, they identified three T cell classes: polarized (Tp), conventional spherical (To), and “stripy” spherical (Tø) with unique nuclear envelope invaginations forming organelle factories. During viral infection, T cells shift from Tø to Tp in the effector phase and revert to Tø in memory cells after 28 days. Tø cells show stronger TCR signaling and form large effector colonies, while To cells divide slower and become memory-like. These findings underscore the role of T cell architecture and advanced image processing in determining cell fate, offering potential improvements in infection protection and undisturbed sorting of effective cells for disease treatment.

🎉 Another week, another post in our new 𝑾𝒉𝒂𝒕 𝑰𝒇 series! ❓ Ever wondered how the human heart develops and organises itself into such a complex, specialised organ? What if we can now unravel the intricacies of this process using advanced single cell and spatial transcriptomics? Elie. N. Farah and colleagues shed light on the cellular organisation and diversity of the developing human heart in their paper published in Nature on the 13th of March 2024. 𝐖𝐡𝐚𝐭 𝐝𝐢𝐝 𝐭𝐡𝐞𝐲 𝐝𝐨? ✔ Performed single cell RNA sequencing on developing human hearts to establish a cell atlas. ✔ Investigated cell neighbourhoods in the developing human heart with Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH). 𝐖𝐡𝐚𝐭 𝐝𝐢𝐝 𝐭𝐡𝐞𝐲 𝐝𝐢𝐬𝐜𝐨𝐯𝐞𝐫? ✔ Single cell RNA sequencing could segregate cells into 5 distinct compartments- cardiomyocyte, mesenchymal, endothelial, neuronal and blood. ✔ Further clustering analyses identified intra- compartmental cellular heterogeneity corresponding to their anatomical location and development stage, providing unique insight into cardiac developmental complexity. ✔ Cells in different anatomical regions of the heart were spatially distinct from each other, with greater cellular complexity in the ventricle compared to the atrium. ✔ Diverse cardiac cells were found to associate with each other in cell communities that were distinct in each anatomical region. These cell communities appeared to form based on the functional requirement of the region. ✔ Ventricle development was particularly complex, involving a complicated multicellular interaction between cardiomyocytes, fibroblasts, and endothelial cells. Overall, this paper presents a detailed molecular and spatial cell atlas of the developing human heart. The data are extremely valuable to understand the pathological mechanisms of congenital and adult heart diseases and can inform future tissue engineering efforts to produce multicellular heart tissue for cardiac repair. 𝐂𝐢𝐭𝐚𝐭𝐢𝐨𝐧: Farah, E.N., Hu, R.K., Kern, C. et al. Spatially organized cellular communities form the developing human heart. Nature (2024). https://lnkd.in/eNJ9wkZX At BioMed X Institute, we use single cell RNA sequencing, spatial transcriptomics, and spatial proteomics tools to understand the cellular architecture of the human synovium in rheumatoid arthritis and the immune landscape of the human gut. These technologies enable the generation of new knowledge and drive our innovative preclinical research programme. 𝐅𝐢𝐧𝐝 𝐨𝐮𝐭 𝐦𝐨𝐫𝐞 𝐚𝐛𝐨𝐮𝐭 𝐨𝐮𝐫 𝐫𝐞𝐬𝐞𝐚𝐫𝐜𝐡 𝐭𝐞𝐚𝐦𝐬 𝐡𝐞𝐫𝐞: 𝐓𝐞𝐚𝐦 𝐏𝐓𝐀- https://lnkd.in/eXD5ep4E 𝐓𝐞𝐚𝐦 𝐓𝐌𝐈- https://lnkd.in/e6tAAMw5 #MERFISH #scRNAseq #cardiacdevelopment 

Dormant cells found in the retina could be the key to a breakthrough method that allows doctors to restore vision in humans. Degenerative retinal disease is a huge problem for millions of people. However, new research could help combat the death of photoreceptors that help drive this disease by transforming dormant support neurons into tissue that works similarly to cells called cone photoreceptors. Photoreceptors are light-sensitive cells found in the back of the eye. However, when they die, and the person has a degenerative retinal disease, the cells aren’t replaced, making it harder for light to enter the eye and do what is needed. As such, utilizing dormant cells to replace those dead photoreceptors could open the door for some intriguing new treatment options. These neurons are called Müller glial cells, and the reason that they caught scientists’ eyes is that they have shown the ability to be reprogrammed in some animals. They can’t quite do that in humans, but the researchers managed to get them to pick up some crucial functions that let them act as photoreceptors. It isn’t quite the same as replacing the cell, but it could help restore vision in some humans. This research is very much in its early days, and we’ve seen other attempts to help blind people see in the past with some astonishing results. If scientists can further develop this idea, though, they may be able to get the neuron cells to transform more reliably, making it easier for them to act as photoreceptors in the retina, thereby restoring vision by replacing the damaged cells. Of course, we’ll have to wait to see exactly how this research continues down the line, but for now, it is fascinating to see what these researchers have accomplished. A study on their findings has been published in PNAS. https://lnkd.in/gJ-2pFST

The microgravity environment of the International Space Station induces physiological changes in cardiac cells not only at the organ level but also at the cellular level. Discover how human induced #pluripotent #stemcells can be transformed into cardiac cells and sent to space for use in disease modeling, drug screening, and #regenmed in the latest issue of #Upward, the official magazine of the ISS National Lab. #heartdisease #iPSC

In these short RNAs, they identified sequences that when present kill cells by blocking the production of proteins necessary for cells’ survival. The data suggests that these toxic short RNAs contribute to neuron death. However, their activity is typically curtailed by protective RNAs such as microRNAs which prevent the toxic ones from disrupting the cell’s machinery. The numbers of protective RNAs decrease with aging allowing the toxic short RNAs to take over. Ideally, finding ways to increase the number of protective RNAs would result in better outcomes for brain cells. This is borne out by data from the brains of Super Agers, individuals aged 80 and older who have the memory capacity of people who are 20 to 30 years younger. The analysis indicated that Super Agers have higher amounts of the protective short RNA strands in their brain cells, according to the team. https://lnkd.in/g_3-p-NB

Cell Surface RNAs Recruit Neutrophils to Inflammatory Sites

In preparation for future space missions, simulated microgravity bioreactors, such as random positioning machines (RPM), represent an important part of ground facilities in microgravity research. When performing an experiment using the RPM with adherent cell populations, it works under the principle that over time, the gravity vector is averaged to microgravity levels, which causes the cells to feel microgravity conditions.  However, a proper gravisensor have not yet been identified in non-specialized human cells. In this study, we attempted to establish the role of the RPM in microgravity research using human cells. Our experiments show that an adherent cell population exposed to randomization of the gravity vector using an RPM may not only experience simulated microgravity. Other stimuli, such as the shear forces generated by the fluid dynamics of the cell culture medium, may play a bigger role in the commonly observed cellular effects. Exposing the cells to shear stress in a similar range of the RPM using a fluid flow experiment, we observed similar molecular changes to those obtained in the adherent cell population exposed to RPM.  The use of a control group under shear stress conditions should now be considered when working with simulated microgravity bioreactors and can help to distinguish the effects of microgravity over the cells. Thank you to ibidi GmbH for the immense support during the shear stress experiments with the Ibidi Pump System. Finally, we argue that for a human cell, the gravitational vector may be less important in comparison to the local microenvironment.  Non-specialized human cells may only sense changes in the gravity vector indirectly and not with a direct gravisensor inside them. We think it is worthwhile to mention Einstein’s point about gravity:  “ The gravitational field has only a relative existence. Thus, for an observer falling freely from the roof of a house, there exists, during his fall, no gravitational field”. This paper attempts to pave the way for determining a precise role for the use of simulated microgravity bioreactors such as the RPM in biological research, in preparation for future space experiments. In summary, the RPM serves as a simulator of microgravity by randomizing the impact of the gravity vector, especially for suspension (i.e., detached) cells. Simultaneously, it simulates physiological shear forces on the adherent cell layer. The RPM thus offers a unique combination of environmental conditions for in vitro cancer research. We thank the entire team for their contribution, ideas, and effort in this research article. Congratulations to all of you :) Marcus Krüger, Daniela Melnik, Viviann Sandt, Shannon Marchal, Marco Calvaruso, Ian Johnson, Simon Wüest, Daniela Grimm, Stefan Kahlert

The coordination of the immune cell response and the movement of key cells involved is like a highly choreographed dance. The sensing of an antigen and its presentation to lymph nodes is the responsibility of dendritic cells. It was initially thought that their migration was a passive process, where they followed chemokine gradients like blood hounds on a trail. Fascinating new research published this week demonstrates how dendritic cells play a much more active role in controlling and generating their own chemokine gradients to not only guide their own movements but those of other immune cells. The authors used a combination of sophisticated 3D live cell imaging and computational models to show how dendritic cells endocytose the chemokine CCR7, self-shaping a gradient which guided their movement and was detected by T-cells. The immune system continues to prove just how complex the interplay is between chemical signals, immune cells and their subsequent responses. Read the paper here: https://lnkd.in/exn7dgYF

All molecules, structures, cells of organisms are subject to destruction in the process of vital activity. In the organisms of multicellular animals and humans, the process of regeneration is always taking place: the destruction of old cells and their replacement with new ones. Cells are replaced even if the cells are in perfect condition. The earlier the body destroys the matured cells and replaces them with new ones , the younger the body is (the higher the rate of regeneration). Stem cells are the precursor cells of all differentiated cells. Asymmetric division of the mother stem cell gives rise to one, analogue of the mother, daughter cell and another daughter cell that follows a further differentiation pathway. Despite such asymmetric division, the pool of stem cells decreases over time. Moreover, the intervals between stem cell divisions are increasing. The combination of these two processes leads to a decrease in the rate of regeneration and ageing of the organism. During asymmetric division of stem cells, daughter cells, with preserved stem cell potency, selectively retain mother (old) centrioles. Unlike nuclear DNA molecules, repairs do not occur in centrioles. Hypothetically, old centrioles are more susceptible to destruction than other cell structures—making centrioles a potentially structure of the ageing of organisms.