Gli1 Defines a Subset of Fibroadipogenic Progenitors that Promote Skeletal Muscle Regeneration with Less Fat Accumulation

Using a lineage tracing mouse model, the authors demonstrated that Gli1 marks a small subset of muscle‐resident fibro‐adipogenic progenitors with elevated Hedgehog signaling.
[Journal of Bone and Mineral Research]
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Targeting the Sonic Hedgehog Pathway to Suppress the Expression of the Cancer Stem Cell (CSC)—Related Transcription Factors and CSC-Driven Thyroid Tumor Growth

Scientists report that inhibition of the sonic hedgehog pathway by Gli1 siRNA or by cyclopamine and GANT61 reduced BMI1 and SOX2 expression in SW1736 and KAT-18 cells, two anaplastic thyroid cancer cell lines.
[Cancers]
Lu, Y., Zhu, Y., Deng, S., Chen, Y., Li, W., Sun, J., & Xu, X. (2021). Targeting the Sonic Hedgehog Pathway to Suppress the Expression of the Cancer Stem Cell (CSC)—Related Transcription Factors and CSC-Driven Thyroid Tumor Growth. Cancers, 13(3), 418. https://doi.org/10.3390/cancers13030418 Cite
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Berberine Inhibits Chemotherapy-Exacerbated Ovarian Cancer Stem Cell-Like Characteristics and Metastasis through GLI1

The authors found that chemotherapy exacerbated the migration and CSC-like characteristics through transcriptional factor GLI1, which regulated the pluripotency-associated gene BMI1 and the epithelial-mesenchymal transition markers Vimentin and Snail.
[European Journal of Pharmacology]
Zhao, Y., Yang, X., Zhao, J., Gao, M., Zhang, M., Shi, T., Zhang, F., Zheng, X., Pan, Y., Shao, D., Li, J., He, K., & Chen, L. (2021). Berberine inhibits chemotherapy-exacerbated ovarian cancer stem cell-like characteristics and metastasis through GLI1. European Journal of Pharmacology, 895, 173887. https://doi.org/10.1016/j.ejphar.2021.173887 Cite
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Long-Term Self-Renewing Stem Cells in the Adult Mouse Hippocampus Identified by Intravital Imaging

Scientists used two-photon microscopy and followed neural stem cells that were genetically labeled through conditional recombination driven by the regulatory elements of the stem cell-expressed genes GLI family zinc finger 1 or achaete-scute homolog 1.
[Nature Neuroscience]
Bottes, S., Jaeger, B. N., Pilz, G.-A., Jörg, D. J., Cole, J. D., Kruse, M., Harris, L., Korobeynyk, V. I., Mallona, I., Helmchen, F., Guillemot, F., Simons, B. D., & Jessberger, S. (2020). Long-term self-renewing stem cells in the adult mouse hippocampus identified by intravital imaging. Nature Neuroscience, 1–9. https://doi.org/10.1038/s41593-020-00759-4 Cite
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Functional Crosstalk between Myeloid Foxo1-β-Catenin Axis and Hedgehog/Gli1 Signaling in Oxidative Stress Response

Researchers report that myeloid-specific Foxo1 knockout (Foxo1M-KO) mice were resistant to oxidative stress-induced hepatocellular damage with reduced macrophage/neutrophil infiltration, and pro-inflammatory mediators in liver ischemia/reperfusion injury.
[Cell Death & Differentiation]
Li, C., Sheng, M., Lin, Y., Xu, D., Tian, Y., Zhan, Y., Jiang, L., Coito, A. J., Busuttil, R. W., Farmer, D. G., Kupiec-Weglinski, J. W., & Ke, B. (2020). Functional crosstalk between myeloid Foxo1–β-catenin axis and Hedgehog/Gli1 signaling in oxidative stress response. Cell Death & Differentiation, 1–15. https://doi.org/10.1038/s41418-020-00695-7 Cite
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ST3GAL1 is a Target of the SOX2-GLI1 Transcriptional Complex and Promotes Melanoma Metastasis through AXL

Investigators report a mechanism regulated by the oncogenic SOX2-GLI1 transcriptional complex driving melanoma invasion through the induction of the sialyltransferase ST3GAL1. Using in vitro and in vivo studies, they demonstrated that ST3GAL1 drove melanoma metastasis.
[Nature Communications]
Pietrobono, S., Anichini, G., Sala, C., Manetti, F., Almada, L. L., Pepe, S., Carr, R. M., Paradise, B. D., Sarkaria, J. N., Davila, J. I., Tofani, L., Battisti, I., Arrigoni, G., Ying, L., Zhang, C., Li, H., Meves, A., Fernandez-Zapico, M. E., & Stecca, B. (2020). ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL. Nature Communications, 11(1), 5865. https://doi.org/10.1038/s41467-020-19575-2 Cite
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Gli1+ Mesenchymal Stromal Cells Form a Pathological Niche to Promote Airway Progenitor Metaplasia in the Fibrotic Lung

Scientists showed that Gli1+ MSCs, previously shown to contribute to myofibroblasts during scarring, promoted metaplastic differentiation of airway progenitors into KRT5+ basal cells.
[Nature Cell Biology]
Cassandras, M., Wang, C., Kathiriya, J., Tsukui, T., Matatia, P., Matthay, M., Wolters, P., Molofsky, A., Sheppard, D., Chapman, H., & Peng, T. (2020). Gli1 + mesenchymal stromal cells form a pathological niche to promote airway progenitor metaplasia in the fibrotic lung. Nature Cell Biology, 1–12. https://doi.org/10.1038/s41556-020-00591-9 Cite
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AP-1 and TGFß Cooperativity Drives Non-Canonical Hedgehog Signaling in Resistant Basal Cell Carcinoma

The authors used single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlated with myocardin-related transcription factor (nMRTF) and resistance to Smoothened inhibitors. The nMRTF cell state resembled transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation.
[Nature Communications]
Yao, C. D., Haensel, D., Gaddam, S., Patel, T., Atwood, S. X., Sarin, K. Y., Whitson, R. J., McKellar, S., Shankar, G., Aasi, S., Rieger, K., & Oro, A. E. (2020). AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma. Nature Communications, 11(1), 5079. https://doi.org/10.1038/s41467-020-18762-5 Cite
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Transient Activation of the Hedgehog-Gli Pathway Rescues Radiotherapy-Induced Dry Mouth via Recovering Salivary Gland Resident Macrophages

Researchers showed in mice that activation of canonical Gli-dependent Hedgehog signaling by Gli1 gene transfer was sufficient to recover salivary function impaired by irradiation.
[Cancer Research]
Zhao, Q., Zhang, L., Hai, B., Wang, J., Baetge, C. L., Deveau, M. A., Kapler, G. M., Feng, J. Q., & Liu, F. (2020). Transient activation of the Hedgehog-Gli pathway rescues radiotherapy-induced dry mouth via recovering salivary gland resident macrophages. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0503 Cite
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Berberine Inhibits Colorectal Tumor Growth by Suppressing SHH Secretion

Berberine promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth.
[Acta Pharmacologica Sinica]
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Combined Inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 Pathways Suppresses Breast Cancer Stem Cells, Tumor Growth, and Metastasis

Investigators showed that novel combinations of JAK2 inhibitors with SMO inhibitors synergistically inhibited in vitro growth of TNBC and HER2-positive trastuzumab-resistant BT474-TtzmR cells.
[Oncogene]
Doheny, D., Sirkisoon, S., Carpenter, R. L., Aguayo, N. R., Regua, A. T., Anguelov, M., Manore, S. G., Arrigo, A., Jalboush, S. A., Wong, G. L., Yu, Y., Wagner, C. J., Chan, M., Ruiz, J., Thomas, A., Strowd, R., Lin, J., & Lo, H.-W. (2020). Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis. Oncogene, 1–17. https://doi.org/10.1038/s41388-020-01454-1 Cite
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