Epigenetic and Transcriptional Dynamics of Notch Program in Intestinal Differentiation.

The equilibrium between stem cell self-renewal and differentiation followed by proper lineage specification of progenitor cells is considered imperative for maintaining intestinal homeostasis. In the hierarchical model, intestinal differentiation is defined by the stepwise acquisition of lineage-specific mature cell features, where Notch signaling and lateral inhibition instructively regulate the cell-fate decisions. Recent studies reveal a broadly permissive intestinal chromatin underlies the lineage plasticity and adaptation to diet mediated by Notch transcriptional program.

Identifying Cell-Type-Specific Metabolic Signatures Using Transcriptome and Proteome Analyses.

Studies in various tissues have revealed a central role of metabolic pathways in regulating adult stem cell function in tissue regeneration and tumor initiation. The unique metabolic dependences or preferences of adult stem cells, therefore, are emerging as a new category of therapeutic target. Recently, advanced methods including high-resolution metabolomics, proteomics, and transcriptomics have been developed to address the growing interest in stem cell metabolism.

Live Visualization of ERK Activity in the Mouse Blastocyst Reveals Lineage-Specific Signaling Dynamics.

FGF/ERK signaling is crucial for the patterning and proliferation of cell lineages that comprise the mouse blastocyst. However, ERK signaling dynamics have never been directly visualized in live embryos. To address whether differential signaling is associated with particular cell fates and states, we generated a targeted mouse line expressing an ERK-kinase translocation reporter (KTR) that enables live quantification of ERK activity at single-cell resolution.

Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development.

Precise control and maintenance of population size is fundamental for organismal development and homeostasis. The three cell types of the mammalian blastocyst are generated in precise proportions over a short time, suggesting a mechanism to ensure a reproducible outcome. We developed a minimal mathematical model demonstrating growth factor signaling is sufficient to guarantee this robustness and which anticipates an embryo's response to perturbations in lineage composition.