The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo

Maternal and zygotic activities of the homeodomain protein PAL-1 specify the identity and maintain the development of the multipotent C blastomere lineage in the C. elegans embryo. To identify PAL-1 regulatory target genes, we used microarrays to compare transcript abundance in wild-type embryos with mutant embryos lacking a C blastomere and to mutant embryos with extra C blastomeres. pal-1-dependent C-lineage expression was verified for select candidate target genes by reporter gene analysis, though many of the target genes are expressed in additional lineages as well. The set of validated target genes includes 12 transcription factors, an uncharacterized wingless ligand and five uncharacterized genes. Phenotypic analysis demonstrates that the identified PAL-1 target genes affect specification, differentiation and morphogenesis of C-lineage cells. In particular, we show that cell fate-specific genes (or tissue identity genes) and a posterior HOX gene are activated in lineage-specific fashion. Transcription of targets is initiated in four temporal phases, which together with their spatial expression patterns leads to a model of the regulatory network specified by PAL-1

On Reasoning with RDF Statements about Statements using Singleton Property Triples

The Singleton Property (SP) approach has been proposed for representing and querying metadata about RDF triples such as provenance, time, location, and evidence. In this approach, one singleton property is created to uniquely represent a relationship in a particular context, and in general, generates a large property hierarchy in the schema. It has become the subject of important questions from Semantic Web practitioners. Can an existing reasoner recognize the singleton property triples? And how? If the singleton property triples describe a data triple, then how can a reasoner infer this data triple from the singleton property triples? Or would the large property hierarchy affect the reasoners in some way? We address these questions in this paper and present our study about the reasoning aspects of the singleton properties. We propose a simple mechanism to enable existing reasoners to recognize the singleton property triples, as well as to infer the data triples described by the singleton property triples. We evaluate the effect of the singleton property triples in the reasoning processes by comparing the performance on RDF datasets with and without singleton properties. Our evaluation uses as benchmark the LUBM datasets and the LUBM-SP datasets derived from LUBM with temporal information added through singleton properties

Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo.

In this study, we have developed highly expandable neural stem cells (NSCs) from HESCs and iPSCs that artificially express the oligodendrocyte (OL) specific transcription factor gene Zfp488. This is enough to restrict them to an exclusive oligodendrocyte progenitor cell (OPC) fate during differentiation in vitro and in vivo. During CNS development, Zfp488 is induced during the early stages of OL generation, and then again during terminal differentiation of OLs. Interestingly, the human ortholog Znf488, crucial for OL development in human, has been recently identified to function as a dorsoventral pattering regulator in the ventral spinal cord for the generation of P1, P2/pMN, and P2 neural progenitor domains. Forced expression of Zfp488 gene in human NSCs led to the robust generation of OLs and suppression of neuronal and astrocyte fate in vitro and in vivo. Zfp488 expressing NSC derived oligodendrocytes are functional and can myelinate rat dorsal root ganglion neurons in vitro, and form myelin in Shiverer mice brain in vivo. After transplantation near a site of demyelination, Zfp488 expressing hNSCs migrated to the lesion and differentiated into premyelinating OLs. A certain fraction also homed in the subventricular zone (SVZ). Zfp488-ZsGreen1-hNSC derived OLs formed compact myelin in Shiverer mice brain seen under the electron microscope. Transplanted human neural stem cells (NSC) that have the potential to differentiate into functional oligodendrocytes in response to remyelinating signals can be a powerful therapeutic intervention for disorders where oligodendrocyte (OL) replacement is beneficial

Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics.

Our knowledge of transcriptional heterogeneities in epithelial stem and progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem and progenitor potential, but a comprehensive dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell state in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses predict a quasi-linear differentiation hierarchy where basal cells progress from Col17a1Hi/Trp63Hi state to early-response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal transcriptional states. Our study provides a systematic view of epidermal cellular dynamics, supporting a revised "hierarchical-lineage" model of homeostasis

Quantitative Perspectives on Fifty Years of the Journal of the History of Biology

Journal of the History of Biology provides a fifty-year long record for examining the evolution of the history of biology as a scholarly discipline. In this paper, we present a new dataset and preliminary quantitative analysis of the thematic content of JHB from the perspectives of geography, organisms, and thematic fields. The geographic diversity of authors whose work appears in JHB has increased steadily since 1968, but the geographic coverage of the content of JHB articles remains strongly lopsided toward the United States, United Kingdom, and western Europe and has diversified much less dramatically over time. The taxonomic diversity of organisms discussed in JHB increased steadily between 1968 and the late 1990s but declined in later years, mirroring broader patterns of diversification previously reported in the biomedical research literature. Finally, we used a combination of topic modeling and nonlinear dimensionality reduction techniques to develop a model of multi-article fields within JHB. We found evidence for directional changes in the representation of fields on multiple scales. The diversity of JHB with regard to the representation of thematic fields has increased overall, with most of that diversification occurring in recent years. Drawing on the dataset generated in the course of this analysis, as well as web services in the emerging digital history and philosophy of science ecosystem, we have developed an interactive web platform for exploring the content of JHB, and we provide a brief overview of the platform in this article. As a whole, the data and analyses presented here provide a starting-place for further critical reflection on the evolution of the history of biology over the past half-century.Comment: 45 pages, 14 figures, 4 table