Search results for "cell fate"
showing 10 items of 75 documents
Dual Function Molecules and Processes in Cell Fate Decision: A Preface to the Special Issue
2020
A lot of water has passed under the bridge since 1999, when C.J. Jeffery stated in a pioneering review that “the idea of one gene-one protein-one function has become too simple” [...]
AP2α controls the dynamic balance between miR-126&126* and miR-221&222 during melanoma progression
2016
Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumor suppressors miR-126&126∗ in melanoma development and progression. According to the inverse correlation between endogenous miR-221&222 and miR-126&126∗, respectively increasing or decreasing with malignancy, their enforced expression or silencing was sufficient for a reciprocal regulation. In line with the opposite roles of these miRs, protein analyses confirmed the reverse ex…
Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?
2016
Irreversible functional deficits in multiple sclerosis (MS) are directly correlated to axonal damage and loss. Neurodegeneration results from immune-mediated destruction of myelin sheaths and subsequent axonal demyelination. Importantly, oligodendrocytes, the myelinating glial cells of the central nervous system, can be replaced to some extent to generate new myelin sheaths. This endogenous regeneration capacity has so far mainly been attributed to the activation and recruitment of resident oligodendroglial precursor cells. As this self-repair process is limited and increasingly fails while MS progresses, much interest has evolved regarding the development of remyelination-promoting strateg…
Rabphilin involvement in filtration and molecular uptake in Drosophila nephrocytes suggests a similar role in human podocytes
2020
ABSTRACT Drosophila nephrocytes share functional, structural and molecular similarities with human podocytes. It is known that podocytes express the rabphilin 3A (RPH3A)-RAB3A complex, and its expression is altered in mouse and human proteinuric disease. Furthermore, we previously identified a polymorphism that suggested a role for RPH3A protein in the development of urinary albumin excretion. As endocytosis and vesicle trafficking are fundamental pathways for nephrocytes, the objective of this study was to assess the role of the RPH3A orthologue in Drosophila, Rabphilin (Rph), in the structure and function of nephrocytes. We confirmed that Rph is required for the correct function of the en…
Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells.
2016
Muschaweckh et al. show that antigen presentation in the skin regulates the generation of tissue-resident memory T (TRM) cells by orchestrating local competition of antiviral CD8+ T cells, revealing a mechanism to fine-tune the repertoire of regional pools of TRM cells.
Notch and TLR signaling coordinate monocyte cell fate and inflammation
2020
AbstractConventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of …
Fetal neurogenesis: breathe HIF you can.
2016
Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, s…
Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo
2016
Summary - The realization that nuclear distribution of DNA, RNA, and proteins differs between cell types and developmental stages suggests that nuclear organization serves regulatory functions. Understanding the logic of nuclear architecture and how it contributes to differentiation and cell fate commitment remains challenging. Here, we use soft X-ray tomography (SXT) to image chromatin organization, distribution, and biophysical properties during neurogenesis in vivo. Our analyses reveal that chromatin with similar biophysical properties forms an elaborate connected network throughout the entire nucleus. Although this interconnectivity is present in every developmental stage, differentiati…
Scabrous overexpression in the eye affects R3/R4 cell fate specification and inhibits notch signaling
2015
Background Planar cell polarity (PCP) in the Drosophila eye is generated when immature ommatidial preclusters acquire opposite chirality in the dorsal and ventral halves of the eye imaginal disc and rotate 90 ° toward the equator. The scabrous (sca) gene is involved in R8 differentiation and in the correct spacing of ommatidial clusters in eye imaginal discs, but it was also suggested to be required during ommatidial rotation. However, no clear relationships between sca and other genes involved in the process were established. Results To explore the role of Sca in PCP establishment, we performed an RNAi-based modifier genetic screen using the rough eye phenotype of sca-overexpressing flies.…
Nucleocytoplasmic transport of the RNA-binding protein CELF2 regulates neural stem cell fates.
2020
The development of the cerebral cortex requires balanced expansion and differentiation of neural stem/progenitor cells (NPCs), which rely on precise regulation of gene expression. Because NPCs often exhibit transcriptional priming of cell-fate-determination genes, the ultimate output of these genes for fate decisions must be carefully controlled in a timely fashion at the post-transcriptional level, but how that is achieved is poorly understood. Here, we report that de novo missense variants in an RNA-binding protein CELF2 cause human cortical malformations and perturb NPC fate decisions in mice by disrupting CELF2 nucleocytoplasmic transport. In self-renewing NPCs, CELF2 resides in the cyt…