TGFβ Promotes Widespread Enhancer Chromatin Opening and Operates on Genomic Regulatory Domains

Researchers report that Transforming Growth Factor-β (TGFβ) treatment triggered fast and widespread increase in chromatin accessibility in about 80% of the enhancers of normal mouse mammary epithelial-gland cells, irrespective of whether they were activated, repressed or not regulated by TGFβ.
[Nature Communications]
Guerrero-Martínez, J. A., Ceballos-Chávez, M., Koehler, F., Peiró, S., & Reyes, J. C. (2020). TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains. Nature Communications, 11(1), 6196. https://doi.org/10.1038/s41467-020-19877-5 Cite
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Interleukin-11 Signaling Underlies Fibrosis, Parenchymal Dysfunction, and Chronic Inflammation of the Airway

Initially thought of as a protective cytokine, interleukin-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.
[Experimental and Molecular Medicine]
Ng, B., Cook, S. A., & Schafer, S. (2020). Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway. Experimental & Molecular Medicine, 1–8. https://doi.org/10.1038/s12276-020-00531-5 Cite
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The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis

Colorectal cancer (CRC) tumoroids and a mouse model of CRC hepatic metastasis were used to test approaches to modify bone morphogenetic protein signaling and treat CRC.
[Gastroenterology]
Kobayashi, H., Gieniec, K. A., Wright, J. A., Wang, T., Asai, N., Mizutani, Y., Ida, T., Ando, R., Suzuki, N., Lannagan, T. R., Ng, J. Q., Hara, A., Shiraki, Y., Mii, S., Ichinose, M., Vrbanac, L., Lawrence, M. J., Sammour, T., Uehara, K., … Woods, S. L. (2020). The balance of stromal BMP signaling mediated by GREM1 and ISLR drives colorectal carcinogenesis. Gastroenterology, 0(0). https://doi.org/10.1053/j.gastro.2020.11.011 Cite
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TGFβ Promotes YAP‐Dependent AXL Induction in Mesenchymal‐Type Lung Cancer Cells

Researchers revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, they also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression.
[Molecular Oncology]
Choi, J.-Y., Lee, H., Kwon, E.-J., Kong, H.-J., Kwon, O.-S., & Cha, H.-J. (n.d.). TGFβ promotes YAP-dependent AXL induction in mesenchymal-type lung cancer cells. Molecular Oncology, n/a(n/a). https://doi.org/https://doi.org/10.1002/1878-0261.12857 Cite
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Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche

Investigators found that the source of transforming growth factor-β-supporting resident memory T cells was autocrine.
[Immunity]
Hirai, T., Yang, Y., Zenke, Y., Li, H., Chaudhri, V. K., Diaz, J. S. D. L. C., Zhou, P. Y., Nguyen, B. A.-T., Bartholin, L., Workman, C. J., Griggs, D. W., Vignali, D. A. A., Singh, H., Masopust, D., & Kaplan, D. H. (2020). Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.10.022 Cite
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Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

Scientists focused on the analysis of microenvironmental factors introduced in melanoma heterogeneous spheroids by different dermal fibroblasts.
[Cancers]
Novotný, J., Strnadová, K., Dvořánková, B., Kocourková, Š., Jakša, R., Dundr, P., Pačes, V., Smetana Jr, K., Kolář, M., & Lacina, L. (2020). Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids. Cancers, 12(11), 3324. https://doi.org/10.3390/cancers12113324 Cite
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A Balance Score between Immune Stimulatory and Suppressive Microenvironments Identifies Mediators of Tumour Immunity and Predicts Pan-Cancer Survival

The balance between immune-stimulatory and immune-suppressive mechanisms in the tumour microenvironment is associated with tumour rejection and can predict the efficacy of immune checkpoint-inhibition therapies.
[British Journal of Cancer]
Turan, T., Kongpachith, S., Halliwill, K., Roelands, J., Hendricks, W., Marincola, F. M., Hudson, T. J., Jacob, H. J., Bedognetti, D., Samayoa, J., & Ceccarelli, M. (2020). A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival. British Journal of Cancer, 1–10. https://doi.org/10.1038/s41416-020-01145-4 Cite
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Inhibition of LTβR Signalling Activates WNT-Induced Regeneration in Lung

Scientists demonstrated increased expression of lymphotoxin β-receptor (LTβR) ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTβR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease.
[Nature]
Conlon, T. M., John-Schuster, G., Heide, D., Pfister, D., Lehmann, M., Hu, Y., Ertüz, Z., Lopez, M. A., Ansari, M., Strunz, M., Mayr, C., Ciminieri, C., Costa, R., Kohlhepp, M. S., Guillot, A., Günes, G., Jeridi, A., Funk, M. C., Beroshvili, G., … Yildirim, A. Ö. (2020). Inhibition of LTβR signalling activates WNT-induced regeneration in lung. Nature, 1–6. https://doi.org/10.1038/s41586-020-2882-8 Cite
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Contribution of GATA6 to Homeostasis of the Human Upper Pilosebaceous Unit and Acne Pathogenesis

GATA6, expressed in the upper pilosebaceous unit of normal human skin, is down-regulated in acne. GATA6 controls keratinocyte proliferation and differentiation to prevent hyperkeratinisation of the infundibulum, which is the primary pathological event in acne.
[Nature Communications]
Oulès, B., Philippeos, C., Segal, J., Tihy, M., Vietri Rudan, M., Cujba, A.-M., Grange, P. A., Quist, S., Natsuga, K., Deschamps, L., Dupin, N., Donati, G., & Watt, F. M. (2020). Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis. Nature Communications, 11(1), 5067. https://doi.org/10.1038/s41467-020-18784-z Cite
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Long-Term Helicobacter pylori Infection Switches Gastric Epithelium Reprogramming Towards Cancer Stem Cell-Related Differentiation Program in Hp-Activated Gastric Fibroblast-TGFβ Dependent Manner

TGFβ1 rich secretome from Helicobacter pylori-reprogrammed fibroblasts prompted phenotypic plasticity and epithelial–mesenchymal transition (EMT) of gastric epithelium, inducing pro-neoplastic expansion of post-EMT cells in the presence of low TGFβR1 and TGFβR2 activity.
[Microorganisms]
Krzysiek-Maczka, G., Targosz, A., Szczyrk, U., Wrobel, T., Strzalka, M., Brzozowski, T., Czyz, J., & Ptak-Belowska, A. (2020). Long-Term Helicobacter pylori Infection Switches Gastric Epithelium Reprogramming Towards Cancer Stem Cell-Related Differentiation Program in Hp-Activated Gastric Fibroblast-TGFβ Dependent Manner. Microorganisms, 8(10), 1519. https://doi.org/10.3390/microorganisms8101519 Cite
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Tankyrase Inhibitor XAV-939 Enhances Osteoblastogenesis and Mineralization of Human Skeletal (Mesenchymal) Stem Cells

Researchers investigated the effect of Tankyrase inhibition in osteoblast differentiation of human skeletal MSCs.
[Scientific Reports]
Almasoud, N., Binhamdan, S., Younis, G., Alaskar, H., Alotaibi, A., Manikandan, M., Alfayez, M., Kassem, M., & AlMuraikhi, N. (2020). Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of human skeletal (mesenchymal) stem cells. Scientific Reports, 10(1), 16746. https://doi.org/10.1038/s41598-020-73439-9 Cite
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