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Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth

(2020) CELL. 180(3). p.502-520
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Abstract
The tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers (MADMs), we delineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activated medulloblastomas that originate from unipotent granule neuron progenitors in the brain. First, we found that astrocytes within the TME(TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally never differentiate into astrocytes. Second, we identified that TME-derived IGF1 promotes tumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) is produced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation. Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studies reveal an evolutionary process that produces a multi-lateral network within the TME of medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microglia to produce IGF1 to promote tumor progression.
Keywords
CARCINOMA-ASSOCIATED FIBROBLASTS, CANCER-ASSOCIATED FIBROBLASTS, MOSAIC, ANALYSIS, DOUBLE MARKERS, MACROPHAGE RECRUITMENT, CD11B EXPRESSION, MOUSE MODELS, TNF-ALPHA, IN-VIVO, T-CELLS

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Citation

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MLA
Yao, Maojin, et al. “Astrocytic Trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth.” CELL, vol. 180, no. 3, Cell Press, 2020, pp. 502–20.
APA
Yao, M., Ventura, P. B., Jiang, Y., Rodriguez, F. J., Wang, L., Perry, J. S. A., … Zong, H. (2020). Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth. CELL, 180(3), 502–520.
Chicago author-date
Yao, Maojin, P. Britten Ventura, Ying Jiang, Fausto J. Rodriguez, Lixin Wang, Justin S. A. Perry, Yibo Yang, et al. 2020. “Astrocytic Trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth.” CELL 180 (3): 502–20.
Chicago author-date (all authors)
Yao, Maojin, P. Britten Ventura, Ying Jiang, Fausto J. Rodriguez, Lixin Wang, Justin S. A. Perry, Yibo Yang, Kelsey Wahl, Rowena B. Crittenden, Mariko L. Bennett, Lin Qi, Cong-Cong Gong, Xiao-Nan Li, Ben A. Barres, Timothy P. Bender, Kodi Ravichandran, Kevin A. Janes, Charles G. Eberhart, and Hui Zong. 2020. “Astrocytic Trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth.” CELL 180 (3): 502–520.
Vancouver
1.
Yao M, Ventura PB, Jiang Y, Rodriguez FJ, Wang L, Perry JSA, et al. Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth. CELL. 2020;180(3):502–20.
IEEE
[1]
M. Yao et al., “Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth,” CELL, vol. 180, no. 3, pp. 502–520, 2020.
@article{8662377,
  abstract     = {The tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers (MADMs), we delineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activated medulloblastomas that originate from unipotent granule neuron progenitors in the brain. First, we found that astrocytes within the TME(TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally never differentiate into astrocytes. Second, we identified that TME-derived IGF1 promotes tumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) is produced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation. Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studies reveal an evolutionary process that produces a multi-lateral network within the TME of medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microglia to produce IGF1 to promote tumor progression.},
  author       = {Yao, Maojin and Ventura, P. Britten and Jiang, Ying and Rodriguez, Fausto J. and Wang, Lixin and Perry, Justin S. A. and Yang, Yibo and Wahl, Kelsey and Crittenden, Rowena B. and Bennett, Mariko L. and Qi, Lin and Gong, Cong-Cong and Li, Xiao-Nan and Barres, Ben A. and Bender, Timothy P. and Ravichandran, Kodi and Janes, Kevin A. and Eberhart, Charles G. and Zong, Hui},
  issn         = {0092-8674},
  journal      = {CELL},
  keywords     = {CARCINOMA-ASSOCIATED FIBROBLASTS,CANCER-ASSOCIATED FIBROBLASTS,MOSAIC,ANALYSIS,DOUBLE MARKERS,MACROPHAGE RECRUITMENT,CD11B EXPRESSION,MOUSE MODELS,TNF-ALPHA,IN-VIVO,T-CELLS},
  language     = {eng},
  number       = {3},
  pages        = {502--520},
  publisher    = {Cell Press},
  title        = {Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth},
  url          = {http://dx.doi.org/10.1016/j.cell.2019.12.024},
  volume       = {180},
  year         = {2020},
}

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