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Figure 1. Total Cell Expansion for Fetal Human Telencephalic and Cortical Cells Cultured as Neurospheres with Complete NeuroCult™ Proliferation Medium (Human) Containing rh EGF, rh bFGF and Heparin
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Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy. C. P. Couturier et al. Nature communications 2020 jul
Abstract
Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer's cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.
A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury. R. Gao et al. Pediatric surgery international 2019 dec
Abstract
AIM OF THE STUDY Human breast milk reduces the risk and severity of necrotizing enterocolitis (NEC). Exosomes are extracellular vesicles (EVs) found in high concentrations in milk, and they mediate intercellular communication and immune responses. The aim of this study is to compare the protective effects of exosomes that are derived from different time periods of breast milk production against intestinal injury using an ex vivo intestinal organoid model. METHODS Colostrum, transitional and mature breast milk samples from healthy lactating mothers were collected. Exosomes were isolated using serial ultracentrifugation and filtration. Exosomes' presence was confirmed using transmission electron microscopy (TEM) and western blot. To form the intestinal organoids, terminal ileum was harvested from neonatal mice pups at postnatal day 9, crypts were isolated and organoids were cultured in matrigel. Organoids were either cultured with exposure to lipopolysaccharide (LPS), or in treatment groups where both LPS and exosomes were added in the culturing medium. Inflammatory markers and organoids viability were evaluated. MAIN RESULTS Human milk-derived exosomes were successfully isolated and characterized. LPS administration reduced the size of intestinal organoids, induced inflammation through increasing TNF$\alpha$ and TLR4 expression, and stimulated intestinal regeneration. Colostrum, transitional and mature human milk-derived exosome treatment all prevented inflammatory injury, while exosomes derived from colostrum were most effective at reducing inflammatory cytokine. CONCLUSIONS Human breast milk-derived exosomes were able to protect intestine organoids against epithelial injury induced by LPS. Colostrum exosomes offer the best protective effect among the breast-milk derived exosomes. Human milk exosomes can be protective against the development of intestinal injury such as that seen in NEC.
BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma R. Sachdeva et al. Scientific Reports 2019 dec
Abstract
Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-$\beta$ (TGF-$\beta$) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-$\beta$ signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy.
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Legal Statement: Sold under license from StemCells California, Inc. US Patent Nos. 5,750,376; 5,851,832; 5,980,885; 5,968,829; 5,981,165; 6,071,889; 6,093,531; 6,103,530; 6,165,783; 6,238,922. PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.