Tracking the gene expression programs and clonal relationships that underlie mast, myeloid, and T lineage specification from stem cells.

T cells develop from hematopoietic progenitors in the thymus and protect against pathogens and cancer. However, the emergence of human T cell-competent blood progenitors and their subsequent specification to the T lineage have been challenging to capture in real time. Here, we leveraged a pluripotent stem cell differentiation system to understand the transcriptional dynamics and cell fate restriction events that underlie this critical developmental process.

Cognitive Intra-individual Variability in Cognitively Healthy APOE ε4 Carriers, Mild Cognitive Impairment, and Alzheimer's Disease: a Meta-analysis.

Intra-individual variability (IIV) quantifies an individual's scatter in performances across a test battery (dispersion) or across reaction times within a single task (consistency). No studies have meta-analyzed the cross-sectional IIV literature in those with mild cognitive impairment (MCI) and Alzheimer's dementia (AD). An additional aim of this meta-analysis was to examine IIV in APOE ε4 + healthy control (HC) samples.

Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark.

Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create "Benchmark" to critically evaluate existing tools and find that most function sub-optimally.

Near-perfect precise on-target editing of human hematopoietic stem and progenitor cells.

Precision gene editing in primary hematopoietic stem and progenitor cells (HSPCs) would facilitate both curative treatments for monogenic disorders as well as disease modelling. Precise efficiencies even with the CRISPR/Cas system, however, remain limited. Through an optimization of guide RNA delivery, donor design, and additives, we have now obtained mean precise editing efficiencies >90% on primary cord blood HSCPs with minimal toxicity and without observed off-target editing.