Luis J. Castro-Vega @luiscastro-vega

cGAS-STING are responsible for premature aging of telomerase-deficient zebrafish | The EMBO Journal imageimageTelomere erosion is a hallmark of aging, yet its downstream mechanisms and impact on organismal aging remain unclear. This study shows that cGAS-STING inflammatory signaling drives premature...

www.embopress.org/doi/full/10....

01.09.2025 17:03 — 👍 3 🔁 1 💬 0 📌 0

Spatial transcriptomics reveals human cortical layer and area specification - Nature Multiplexed error-robust fluorescence in situ hybridization (MERFISH) together with deep-learning-based nucleus segmentation enabled the construction of a highly detailed and informative spatially res...

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

15.05.2025 13:22 — 👍 1 🔁 0 💬 0 📌 0

Embryonic macrophages orchestrate niche cell homeostasis for the establishment of the definitive hematopoietic stem cell pool - Nature Communications Haematopoietic stem cells (HSC) are responsible for blood cell generation and reside in the bone marrow. Here, the authors show that macrophages in the bone marrow originate from embryonic or adult ha...

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

14.05.2025 20:35 — 👍 0 🔁 0 💬 0 📌 0

Three-dimensional genome landscape of primary human cancers - Nature Genetics This study characterizes the three-dimensional (3D) genome architecture of 15 primary human cancer types from The Cancer Genome Atlas. The analyses identify different archetypes of enhancer usage and ...

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

12.05.2025 20:17 — 👍 1 🔁 0 💬 0 📌 0

Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1+ microglia Replacing brain macrophages holds substantial therapeutic promise but remains challenging. Bastos et al. uncover the requirements for monocytes to replace microglia and border-associated macrophages. ...

www.cell.com/immunity/ful...

01.05.2025 15:30 — 👍 1 🔁 0 💬 0 📌 0

Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease - Nature The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

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

24.04.2025 13:10 — 👍 0 🔁 0 💬 0 📌 0

YouTube video by Satija Lab Single Cell Genomics Day 2025

youtu.be/kirpoxh6GWQ

23.04.2025 06:49 — 👍 0 🔁 0 💬 0 📌 0

Unified molecular approach for spatial epigenome, transcriptome, and cell lineages | PNAS Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requireme...

www.pnas.org/doi/abs/10.1...

23.04.2025 06:25 — 👍 0 🔁 0 💬 0 📌 0

Integrator loss leads to dsRNA formation that triggers the integrated stress response Integrator (INT) prevents the escape of immature RNAPII to ensure full-length mRNA production. INT deficiency causes defects in RNAPII maturation that lead to premature termination, accumulation of im...

www.cell.com/cell/abstrac...

15.04.2025 16:59 — 👍 0 🔁 0 💬 0 📌 0

A factor-based analysis of individual human microglia uncovers regulators of an Alzheimer-related transcriptional signature Human microglial heterogeneity is only beginning to be appreciated at the molecular level. Here, we present a large, single-cell atlas of expression signatures from 441,088 live microglia broadly samp...

www.biorxiv.org/content/10.1...

31.03.2025 10:49 — 👍 0 🔁 0 💬 0 📌 0

Transient loss of Polycomb components induces an epigenetic cancer fate - Nature A transient perturbation of transcriptional silencing mediated by Polycomb proteins is sufficient to induce an epigenetic cancer cell fate in Drosophila in the absence of driver mutations.

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

30.03.2025 01:47 — 👍 0 🔁 0 💬 0 📌 0

TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states - Nature Cancer Panzeri et al. use a Trim28+/D9 mouse model with intrinsic developmental heterogeneity to show that ‘heavy’ and ‘light’ developmental morphs exhibit different timing, type and severity of cancer, link...

www.nature.com/articles/s43...

30.03.2025 01:30 — 👍 0 🔁 0 💬 0 📌 0

OGT prevents DNA demethylation and suppresses the expression of transposable elements in heterochromatin by restraining TET activity genome-wide - Nature Structural & Molecular Biology Here the authors show that the disruption of OGT expression in mouse embryonic stem cells unleashes TET activity, causing genome-wide decreases in DNA methylation and increases in 5-hydroxymethylcytos...

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

29.03.2025 21:37 — 👍 0 🔁 0 💬 0 📌 0

Chromatin landscape at cis-regulatory elements orchestrates cell fate decisions in early embryogenesis - Nature Communications Germ layer specification during zygotic genome activation is regulated by chromatin state. Here, the authors use single-cell multiome profiling in Drosophila to show that H3K27me3 and H3K27ac at cis-r...

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

29.03.2025 01:04 — 👍 0 🔁 0 💬 0 📌 0

Reciprocal interactions between glioma and tissue-resident cells fueling tumor progression Gliomas are the most frequent primary brain tumor and are essentially incurable. While nondiffuse gliomas are circumscribed, diffuse gliomas display a…

www.sciencedirect.com/science/arti...

26.03.2025 21:20 — 👍 0 🔁 0 💬 0 📌 0

Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing - Nature Genetics This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and...

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

14.03.2025 21:49 — 👍 0 🔁 0 💬 0 📌 0

Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits Perturb-FISH, a method that combines high-throughput imaging spatial transcriptomics with in situ guide RNA detection, allows for the analysis of molecular and functional states, with spatial resoluti...

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

13.03.2025 13:07 — 👍 2 🔁 0 💬 0 📌 0

Telomeric transposons are pervasive in linear bacterial genomes Eukaryotes have linear DNA and their telomeres are hotspots for transposons, which in some cases took over telomere maintenance. Here we identify several families of independently evolved telomeric tr...

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

08.03.2025 07:48 — 👍 0 🔁 0 💬 0 📌 0

Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing - Nature Genetics This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and...

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

04.03.2025 20:35 — 👍 0 🔁 0 💬 0 📌 0

The Multiomics Blueprint of Extreme Human Lifespan The indexed individual, from now on termed M116, was the world’s oldest verified living person from January 17th 2023 until her passing on August 19th 2024, reaching the age of 117 years and 168 days (<https://www.supercentenarian.com/records.html>). She was a Caucasian woman born on March 4th 1907 in San Francisco, USA, from Spanish parents and settled in Spain since she was 8. A timeline of her life events and her genealogical tree are shown in Supplementary Fig. 1a-b . Although centenarians are becoming more common in the demographics of human populations, the so-called supercentenarians (over 110 years old) are still a rarity. In Catalonia, the historic nation where M116 lived, the life-expectancy for women is 86 years, so she exceeded the average by more than 30 years (<https://www.idescat.cat>). In a similar manner to premature aging syndromes, such as Hutchinson-Gilford Progeria and Werner syndrome, which can provide relevant clues about the mechanisms of aging, the study of supercentenarians might also shed light on the pathways involved in lifespan. To unfold the biological properties exhibited by such a remarkable human being, we developed a comprehensive multiomics analysis of her genomic, transcriptomic, metabolomic, proteomic, microbiomic and epigenomic landscapes in different tissues, as depicted in [Fig. 1a][1] , comparing the results with those observed in non-supercentenarian populations. The picture that emerges from our study shows that extremely advanced age and poor health are not intrinsically linked and that both processes can be distinguished and dissected at the molecular level. ![Fig. 1][2]</img> Fig. 1 Chromosomes and genes. a , Schematic representation of all –omics studied in the supercentenarian. b , Telomeres marked with Cy3 (yellow) in nuclei stained with DAPI (blue) observed in HT-qFISH from M116 and younger women’s PBMCs. Scale bars: 20 µm. c , Telomere length (Kb) calculation (left) and percentage of extremely short telomeres (below the 20th percentile) (right) in M116 (orange) using standard curve from samples previously analyzed (black) and control women (blue) ( Online Methods ). d , Circos plot with chromosomal alterations detected through optical genome mapping in supercentenarian. e , Variants of interest (VOI)-harboring genes found in supercentenarian’s genomic DNA contributing to immune function, cardiovascular health, neuroprotection, metabolism, and DNA dynamics. f , Significantly enriched functions of VOI-harboring genes in the supercentenarian. g , VOI-harbouring genes significantly contributing to enriched functions. h , VOI-harboring genes found in supercentenarian’s genomic and mitochondrial DNA contributing to mitochondrial function. i , Mean fluorescence intensity of TMRE (a marker of mitochondrial membrane potential) and SOX (a marker of mitochondrial superoxide ion) in PBMCs from the supercentenarian (orange) and healthy controls across various ages (gray). Unpaired t-test was used to statistically compare M116 to the mean of all control women. *p < 0.05. ### Competing Interest Statement Dr. Esteller declares past grants from Ferrer International and Incyte and personal fees from Quimatryx and Eucerin, outside the submitted work. [1]: #F1 [2]: pending:yes

www.biorxiv.org/content/10.1...

28.02.2025 22:36 — 👍 0 🔁 0 💬 0 📌 0

Embracing cancer complexity: Hallmarks of systemic disease Cancer is a systemic disease in more than one dimension, in terms of its evolutionary course, direct crosstalk with the microenvironment, and intricate communication with the macro-environment. This b...

www.cell.com/cell/abstrac...

13.02.2025 08:17 — 👍 1 🔁 0 💬 0 📌 0

Aging and Cancer—Inextricably Linked Across the Lifespan Aging (as old man wind) alters the trajectory of cancer (dangerous seas) through changes in the immune system and metabolism (among many others), leading to altered cancer epidemiology, pathogenesis,...

onlinelibrary.wiley.com/doi/10.1111/...

13.02.2025 08:13 — 👍 0 🔁 0 💬 0 📌 0

Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy Peng et al. developed an individualized patient tumor organoid (IPTO) model that closely mirrors the molecular and cellular pathology and tumor microenvironment of primary and metastatic brain cancers...

www.cell.com/cell-stem-ce...

11.02.2025 20:57 — 👍 1 🔁 0 💬 0 📌 0

‘Dark proteins’ hiding in our cells could hold clues to cancer and other diseases The human genome encodes potentially thousands of tiny proteins that were previously overlooked. The search is on to find out what they do.

www.nature.com/articles/d41...

11.02.2025 09:37 — 👍 0 🔁 0 💬 0 📌 0

Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length - Nature Communications Mice models often fail to reflect human telomere biology. Here, the authors engineer a mouse strain with a humanized mTert gene, restoring telomere length regulation to a human-like pattern. This mode...

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

10.02.2025 21:26 — 👍 1 🔁 0 💬 0 📌 0

Quantifying metabolites using structure-switching aptamers coupled to DNA sequencing - Nature Biotechnology Metabolites can be quantified using a combination of aptamers and DNA barcodes.

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

06.02.2025 21:38 — 👍 0 🔁 0 💬 0 📌 0

Great & inspiring talk! Thank you for coming and sharing your science.

31.01.2025 22:23 — 👍 1 🔁 0 💬 0 📌 0

Charting the epitranscriptomic landscape across RNA biotypes using native RNA nanopore sequencing Direct RNA sequencing (DRS) enables systematic profiling of RNA modifications at an unprecedented resolution. Here, Diensthuber and Novoa review key efforts made to date pioneering the use of DRS for ...

www.cell.com/molecular-ce...

19.01.2025 19:35 — 👍 23 🔁 9 💬 0 📌 1

Metabolism-driven chromatin dynamics: Molecular principles and technological advances In this review, Sahu and Lu discuss the recent progress in chromatin-metabolism crosstalk. They summarize our current understanding of the molecular principles by which metabolites influence chromatin...

www.cell.com/molecular-ce...

17.01.2025 08:24 — 👍 1 🔁 0 💬 0 📌 0

Glioblastoma remodelling of human neural circuits decreases survival - Nature High-grade gliomas functionally remodel neural circuits in the human brain, promoting tumour progression and impairing cognition.

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

15.01.2025 16:27 — 👍 3 🔁 0 💬 0 📌 0

Luis J. Castro-Vega

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