SUMMARY
The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133+/GFAP− ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133+/GFAP− quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133+ ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.
In this paper, we study an area localization problem in large scale Underwater Wireless Sensor Networks (UWSNs). The limited bandwidth, the severely impaired channel and the cost of underwater equipment all makes the underwater localization problem very challenging. Exact localization is very difficult for UWSNs in deep underwater environment. We propose a Mobile DETs based efficient 3D multi-power Area Localization Scheme (3D-MALS) to address the challenging problem. In the proposed scheme, the ideas of 2D multi-power Area Localization Scheme(2D-ALS) [6] and utilizing Detachable Elevator Transceiver (DET) are used to achieve the simplicity, location accuracy, scalability and low cost performances. The DET can rise and down to broadcast its position. And it is assumed that all the underwater nodes underwater have pressure sensors and know their z coordinates. The simulation results show that our proposed scheme is very efficient.
Targeting leukemia initiating cells is considered to be an effective way to cure leukemia, for which it is critical to identify novel therapeutic targets. Herein, we demonstrate that CD244, which was initially reported as a key regulator for natural killer cells, is highly expressed on both mouse and human leukemia initiating cells. Upon CD244 knockdown, human leukemia cell lines and primary leukemia cells have markedly impaired proliferation abilities both in vitro and in vivo. Interestingly, the repopulation ability of both mouse and human hematopoietic stem cells is not impaired upon CD244 knockdown. Using an MLL-AF9-induced murine acute myeloid leukemia model, we show that leukemogenesis is dramatically delayed upon CD244 deletion, together with remarkably reduced Mac1+/c-Kit+ leukemia cells (enriched for leukemia initiating cells). Mechanistically, we reveal that CD244 is associated with c-Kit and p27 except for SHP-2 as previously reported. CD244 co-operates with c-Kit to activate SHP-2 signaling to dephosphorylate p27 and maintain its stability to promote leukemia development. Collectively, we provide intriguing evidence that the surface immune molecule CD244 plays an important role in the maintenance of stemness of leukemia initiating cells, but not in hematopoietic stem cells. CD244 may represent a novel therapeutic target for the treatment of acute myeloid leukemia.
BackgroundCD274 (programmed death ligand 1, also known as B7H1) is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1). Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown.MethodsWe established an MLL-AF9-induced acute myeloid leukemia (AML) model with wild-type (WT) and CD274-null mice to elucidate the role of CD274 in the cell fates of LICs, including self-renewal, differentiation, cell cycle, and apoptosis. RNA sequencing was performed to reveal the potential downstream targets, the results of which were further validated both in vitro and in vivo.ResultsIn silico analysis indicated that CD274 level was inversely correlated with the overall survival of AML patients. In Mac-1+/c-Kit+ mouse LICs, CD274 was expressed at a much higher level than in the normal hematopoietic stem cells (HSCs). The survival of the mice with CD274-null leukemia cells was dramatically extended during the serial transplantation compared with that of their WT counterparts. CD274 deletion led to a significant decrease in LIC frequency and arrest in the G1 phase of the cell cycle. Interestingly, CD274 is not required for the maintenance of HSC pool as shown in our previous study. Mechanistically, we demonstrated that the levels of both phospho-JNK and Cyclin D2 were strikingly downregulated in CD274-null LICs. The overexpression of Cyclin D2 fully rescued the loss of function of CD274. Moreover, CD274 was directly associated with JNK and enhanced the downstream signaling to increase the Cyclin D2 level, promoting leukemia development.ConclusionsThe surface immune molecule CD274 plays a critical role in the proliferation of LICs. The CD274/JNK/Cyclin D2 pathway promotes the cell cycle entry of LICs, which may serve as a novel therapeutic target for the treatment of leukemia.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0350-6) contains supplementary material, which is available to authorized users.
In this report, Eperythrozoon leading haemolysis was identified in human blood. A patient with long-term anaemia was selected for blood smear examination and electron microscopy. The microscopic results showed a lot of small organisms attaching on the surface of erythrocytes. The partial 16S rRNA gene was amplified and confirmed as haemoplasma by sequence alignment. Phylogenetic analysis showed it fell in the same cluster with other Eperythrozoon species in haemoplasma group. It was the first time to confirm the haemoplasma infection in human blood by molecular assay combined with microscope. Such infection may be a potential criminal of some cases of human unknown origin anaemia.
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