Emergence of a stage-dependent human liver disease signature with directed differentiation of alpha-1 antitrypsin-deficient iPS cells.

Induced pluripotent stem cells (iPSCs) provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ) in the gene responsible for alpha-1 antitrypsin (AAT) deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells.

Incidence and outcome of atlanto-occipital dissociation at a level 1 trauma centre: a prospective study of five cases within 5 years.

Background: Prospective evaluation of atlanto-occipital dissociations (AODs) at a level 1 trauma centre within 5 years.

Methods: Over a period of 5 years (2005-2009), all CT scans of the skull base and the upper cervical spine due to traumatic injuries were prospectively entered into a database. Furthermore, in cases of confirmed AOD all empirical data were prospectively collected.

Occipital condyle fractures. Prospective follow-up of 31 cases within 5 years at a level 1 trauma centre.

Purpose: Prospective investigation of incidence and outcome of occipital condyle fractures (OCF) in a level 1 trauma centre.

Methods: Over a period of 5 years, we prospectively recorded all cases of OCF, and performed a 1-year post-injury radiological and clinical follow-up using CT imaging, SF-36 and Neck Disability Index, respectively.

Results: A total of 31 patients with OCF were identified.

Search strategies in a human water maze analogue analyzed with automatic classification methods.

Although human spatial cognition is at the focus of intense research efforts, experimental evidence on how search strategies differ among age and gender groups remains elusive. To address this problem, we investigated the interaction between age, sex, and strategy usage within a novel virtual water maze-like procedure (VWM). We studied 28 young adults 20-29 years (14 males) and 30 middle-aged adults 50-59 years (15 males).

Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche.

Endogenous and transplanted neural stem cells (NSC) are highly migratory and display a unique tropism for areas of neuro-pathology. However, signals controlling NSC motility in health and disease are still ill-defined. NSC appear to be intimately associated with the cerebral vasculature and angiogenesis is a hallmark of many neurological disorders.

Comprehensive microRNA profiling reveals a unique human embryonic stem cell signature dominated by a single seed sequence.

Embryonic stem cells are unique among cultured cells in their ability to self-renew and differentiate into a wide diversity of cell types, suggesting that a specific molecular control network underlies these features. Human embryonic stem cells (hESCs) are known to have distinct mRNA expression, global DNA methylation, and chromatin profiles, but the involvement of high-level regulators, such as microRNAs (miRNA), in the hESC-specific molecular network is poorly understood. We report that global miRNA expression profiling of hESCs and a variety of stem cell and differentiated cell types using a novel microarray platform revealed a unique set of miRNAs differentially regulated in hESCs, including numerous miRNAs not previously linked to hESCs.

Neural stem cell transplant survival in brains of mice: assessing the effect of immunity and ischemia by using real-time bioluminescent imaging.

Purpose: To use bioluminescent imaging in a murine transplant model to monitor the in vivo responses of transplanted luciferase-gene-positive neural progenitor cells (NPCs) to host immunity and ischemia.

Materials And Methods: All animal studies were conducted according to institutional guidelines, with approval of the Subcommittee on Research Animal Care. Cranial windows were created in all animals, and all animals underwent NPC (C17.

Adhesive interactions between human neural stem cells and inflamed human vascular endothelium are mediated by integrins.

Understanding the mechanisms by which stem cells home precisely to regions of injury or degeneration is of importance to both basic and applied regenerative medicine. Optimizing regenerative processes may depend on identifying the range of molecules that subserve stem cell trafficking. The "rolling" of extravasating cells on endothelium under conditions of physiological flow is the first essential step in the homing cascade and determines cell adhesion and transmigration.

Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines.

Background: In order to compare the gene expression profiles of human embryonic stem cell (hESC) lines and their differentiated progeny and to monitor feeder contaminations, we have examined gene expression in seven hESC lines and human fibroblast feeder cells using Illumina bead arrays that contain probes for 24,131 transcript probes.

Results: A total of 48 different samples (including duplicates) grown in multiple laboratories under different conditions were analyzed and pairwise comparisons were performed in all groups. Hierarchical clustering showed that blinded duplicates were correctly identified as the closest related samples.

Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway.

Migration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified.

Stem cells: cross-talk and developmental programs.

The thesis advanced in this essay is that stem cells-particularly those in the nervous system-are components in a series of inborn 'programs' that not only ensure normal development, but persist throughout life so as to maintain homeostasis in the face of perturbations-both small and great. These programs encode what has come to be called 'plasticity'. The stem cell is one of the repositories of this plasticity.