The Maus Lab

Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging - PubMed Hematopoietic stem cells (HSC) reside within specialized microenvironments that undergo dynamic changes throughout development and aging to support HSC function. However, the evolving cell-cell commun...

📃By integrating single-cell RNA sequencing datasets, Cong et al. characterize the evolution and interactome of hematopoietic niche from embryonic development to aging. #JournalClub

pubmed.ncbi.nlm.nih.gov/39698109/

Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours - Nature An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Lung cancer reprograms the bone marrow to its advantage.
Hedge et al. ( @miriammerad.bsky.social lab)
show that tumors trigger an NRF2-driven stress response in myeloid precursors, which then suppress anti-tumor immunity. Blocking NRF2 boosts immunotherapy.
#JC
🔗 www.nature.com/articles/s41...

#CCESumSchool25 Day 2 🧬
• Lectures: Fundamental Research, Patient-centered Research, Proteomics
• Workshop: Patient Involvement
• First Poster Session!

@vhio.bsky.social @nkinl.bsky.social @nct-heidelberg.bsky.social @gustaveroussy.fr @ki.se @zwartlab.bsky.social @mauslab.bsky.social

Hear from Aistė Avižaitė, who joined us from Lithuania to explore aging & cancer and grow in translational oncology at @vhio.bsky.social.

▶️https://youtube.com/shorts/q0g6zdywe6s

Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy Epigenetic reinforcement of T cell exhaustion is known to be a major barrier limiting T cell responses during immunotherapy. However, the core epigenetic regulators restricting antitumor immunity duri...

📰 In aging bone marrow, cancerous clones thrive by adapting through mutations. Kang et al. show that giving immune cells the same mutations tilts the balance back—helping them resist exhaustion and fight cancer in this hostile niche. #JournalClub
🔗 www.science.org/doi/10.1126/...

📰Aging disrupts metabolic supply chains, constraining cell renewal. But how do we detect these shortages? In >5000 patients, Tapio et al. show that low ferritin is the best predictor for bone marrow iron. A study with broad implications. hashtag #JournalClub

🔗 ashpublications.org/bloodadvance...

📑Why don’t senescent cells fix their DNA? Daigh et al. (Meyer lab) report that uncoupling mTORC1 from E2F sustains transcription-linked DNA damage in senescence.

#JournalClub

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

TET2 deficiency increases the competitive advantage of hematopoietic stem and progenitor cells through upregulation of thrombopoietin receptor signaling - Nature Communications Clonal hematopoiesis is associated with an increased risk of hematologic and a range of inflammation-related diseases. Here, Yang et al. demonstrate a critical role for aberrant thrombopoietin recepto...

Why do TET2-mutant preleukemic cells outcompete healthy HSCs? Yang et al. show that these cells upregulate MPL (thrombopoietin receptor, TPO-R) signaling, giving a clonal edge; inhibiting this pathway reduces it. #JournalClub
www.nature.com/articles/s41...

Impact of TET2 deficiency on iron metabolism in erythroblasts Sideroblastic anemia is characterized by the presence of ring sideroblasts (RSs), which are caused by iron accumulation in the mitochondria of erythroblasts and are present in both the acquired and co...

Why do ring sideroblasts arise in MDS? Often via SF3B1-driven mitochondrial iron buildup. Inokura et al. tested TET2’s role: Tet2-deficient mice show systemic iron overload, and anemia. No classical RS, but intriguing parallels.
#JournalClub
www.exphem.org/article/S030...

🌱We are delighted to welcome Gloria Ariño from Universidad Europea de Madrid as our third summer intern!🌟

Gloria will explore how aging creates metabolic bottlenecks in the colon and how these shape tumorigenesis.

With Gloria, Laura & Aiste, our summer intern dream team is complete!💪

Spatially organized multicellular immune hubs in human colorectal cancer Single-cell transcriptomics-based co-variation analysis of human colorectal cancer identifies a spatially resolved myeloid-rich inflammatory hub that is shared by mismatch repair-deficient (MMRd) and ...

📑Immunotherapy responses differ markedly between MMR-proficient and -deficient colorectal cancers. A scRNA-seq study of 62 patients by ‪@pelkalab.bsky.social‬ et al. (Hacohen lab) reveals key immune–tumor communication differences that may explain this.
#JournalClub

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

🎯 The Aging and Cancer Lab is not afraid of tough battles — in science or laser tag.

What connects aging and cancer? Can we stop it?

We team up and take aim together at the route causes.. 🔬💥

🌱Excited to welcome Aistė Avižaitė from Lithuania’s
@VU_LT
to the lab this summer!

She’ll be studying how chemotherapy alters metabolism in healthy tissues and how this may drive accelerated aging in childhood cancer survivors.

#Aging #Cancer #SummerIntern

Implausibility of radical life extension in humans in the twenty-first century - Nature Aging In the twentieth century, human life expectancy rose dramatically. Based on the past three decades of observed mortality in the eight countries with the longest-lived populations and in Hong Kong and ...

200 years ago in Barcelona, your 40s meant preparing for death. Today, you might have 40 more years ahead.

But as @sjayolshansky et al. show, most gains came from reducing early death. Further progress depends on tackling aging and its consequences.
#JC

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

🌱 Welcome aboard, Laura!

Joining us this summer from @URV_universitat, Laura Boró García will be exploring how aging and chemotherapy disrupt metabolism and epigenetics in the bone marrow. We’re thrilled to have her with us! 🧬🧪

#Aging #Cancer #SummerIntern

Dietary restriction impacts health and lifespan of genetically diverse mice - Nature Health effects of dietary restriction are uncoupled from longevity.

Longer lives in laboratory conditions may compromise survival in the real world. In a large study on genetically diverse mice, Di Francesco et al. in Jackson Labs show that lifespan extension under caloric restriction doesn’t always improve health.

#JournalClub

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

Dietary restriction impacts health and lifespan of genetically diverse mice - Nature Health effects of dietary restriction are uncoupled from longevity.

Longer lives in laboratory conditions may compromise survival in the real world. In a large study on genetically diverse mice, @DiFrancescoA et al. in @jacksonlab show that lifespan extension under caloric restriction doesn’t always improve health.

#JournalClub
www.nature.com/articles/s41...

In a preprint, Han et al. from @yibinkang’s lab report that cancer cells in bone metastases hijack iron from bone marrow macrophages that normally support red blood cell production — linking anemia to metastatic progression.

#JournalClub

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

What makes a bag of cells become a complex, intelligent being—and what breaks those rules to cause aging and system breakdown?

Donella Meadows’ Thinking in Systems offers a toolkit to understand biology, society, and the economy in their native language: systems.

#LabReads 📚

Apc-mutant cells act as supercompetitors in intestinal tumour initiation - Nature Using experiments in organoids and in vivo in mice, the authors show that Apc-mutant cells act as supercompetitors to initiate the formation of adenomas.

Intestinal stem cells (ISCs) with APC mutations outcompete wild-type ISCs by suppressing Wnt signaling in their neighbors - driving colorectal tumor formation.

Exciting work from Vermeulen lab!

Presented by Marc Guasch @JournalClub
www.nature.com/articles/s41...

Molecular characteristics and clinical implications of TP53 mutations in therapy-related myelodysplastic syndromes - Blood Cancer Journal Blood Cancer Journal - Molecular characteristics and clinical implications of TP53 mutations in therapy-related myelodysplastic syndromes

We are all born with blood cells that could turn into cancer. But aging and chemo don’t just damage cells—they differently pick the bad ones. Chemo favors TP53-mutant clones giving rise to therapy-related MDS.
#JournalClub Ning Huang
www.nature.com/articles/s41...

Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis - Scientific Reports Scientific Reports - Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis

Hereditary hemochromatosis related iron overload accelerates age-related cardiac hypertrophy in a mouse model.

Francesca Cogo #JournalClub

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

Increasing number of young individuals are being diagnosed with colorectal cancer. This week, we hosted medical oncologist Iosune Baraibar, who shared what she at
@vhio.bsky.social, and @danafarber.bsky.social collaborators are doing to understand and act on this epidemic. Honored to work at VHIO.

The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan - Nature Aging Gkioni et al. show that trametinib, which targets the Ras–Mek–Erk pathway, extends lifespan in male and female mice and that co-treatment with the known geroprotector rapamycin additively extends life...

Cellular hypermetabolism drives aging and age-related disease. Gkioni et al. (Partridge lab) show that targeting two independent growth/metabolism regulators synergistically extends lifespan and delays cancer in aging mice.

Mate Maus #JournalClub
www.nature.com/articles/s43...

Defining Stem Cell Dynamics in Models of Intestinal Tumor Initiation Common genetic alterations during tumor initiation in the mouse gut reveal clonal advantages. [Also see Perspective by Bozic and Nowak]

For colon cells to form cancer, they must acquire mutations—but how do early mutant clones expand? Vermeulen et al. use lineage tracing to show that competition with wild-type cells is real, and chance dominates.

Marc Guasch #JournalClub

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

Cell competition promotes metastatic intestinal cancer through a multistage process Microenvironment; Cell biology; Cancer

Krotenberg et al. created fluorescent mixed organoids to study cell competition in colorectal cancer. They show cancer cells actively eliminate wild-type neighbors via JNK signaling to fuel their growth.

Marc Guasch #JournalClub
www.cell.com/iscience/ful...

🚀 Recently, we welcomed Agnese Brischetto as our #JournalClub invited speaker! She shared insights into the biology of psoriasis—an autoimmune skin condition affecting ~3% of the population—along with intriguing findings on potential new treatments.

Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice Bone marrow deficient in a gene frequently mutated in blood cells of elderly humans promotes atherosclerosis in mice.

Atherosclerotic burden drives age-related cardiovascular events. Fuster et al. showed TET2-mutant blood cells—common in the elderly—accelerate atherosclerosis via proinflammatory macrophages. Aging bone marrow may fuel cardiovascular aging.

Ning Huang #JournalClub.
www.science.org/doi/10.1126/...

Activation of lysosomal iron triggers ferroptosis in cancer - Nature Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

Tatiana Cañeque et al. (Rodriguez lab) develop Fento-1, a new molecule that eliminates therapy-resistant CD44⁺ cancer stem cells by targeting lysosomal iron and inducing ferroptosis.

Presented by PhD student Francesca Cogo at #JournalClub.

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

Fascinating study from @miriammerad.bsky.social ’s lab suggests our aging immune system may drive cancer. With age, bone marrow–derived monocyte-lineage cells replace resident lung myeloid cells — fueling tumor growth via IL-1 secretion.

👉https://www.science.org/doi/10.1126/science.adn0327