Intestinal stem cell aging signature reveals a reprogramming strategy to enhance regenerative potential.

The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorithm, we identified a set of key transcription factors (Egr1, Irf1, FosB) that drives molecular and functional differences between old and young states.

infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease.

Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C.

Microarray profiling to analyze the effect of Snai1 loss in mouse intestinal epithelium.

Epithelial stem cells from a variety of tissues have been shown to express genes linked to mesenchymal cell states. The Snail family of transcriptional factors has long been regarded as a marker of mesenchymal cells, however recent studies have indicated an involvement in regulation of epithelial stem cell populations. Snai1 is expressed in the stem cell population found at the base of the mouse small intestinal crypt that is responsible for generating all differentiated cell types of the intestinal epithelium.

A Versatile Strategy for Isolating a Highly Enriched Population of Intestinal Stem Cells.

The isolation of pure populations of mouse intestinal stem cells (ISCs) is essential to facilitate functional studies of tissue homeostasis, tissue regeneration, and intestinal diseases. However, the purification of ISCs has relied predominantly on the use of transgenic reporter alleles in mice. Here, we introduce a combinational cell surface marker-mediated strategy that allows the isolation of an ISC population transcriptionally and functionally equivalent to the gold standard Lgr5-GFP ISCs.

Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.

Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages.

Regulated Wnt/beta-catenin signaling sustains adult spermatogenesis in mice.

The importance of Wnt signaling for postnatal testis function has been previously studied in several mouse models, with chronic pathway disruption addressing its function in Sertoli cells and in postmeiotic germ cells. While chronic beta-catenin deletion in Sertoli cells does not profoundly affect testis development, new data indicate that Wnt signaling is required at multiple stages of spermatogenesis. We used two mouse models that allow acute disruption of Wnt signaling to explore the importance of regulated Wnt pathway activity for normal germ cell development in adult male mice.

Regulation of intestinal stem cells by Wnt and Notch signalling.

The mammalian intestine is lined by an epithelial cell layer that is constantly renewed via a population of stem cells that reside in a specialised niche within intestinal crypts. The recent development of tools that permit genetic manipulation and lineage tracing of cells in vivo combined with culture methods in vitro has made the intestine particularly amenable for the study of signals that regulate stem cell function. Both Wnt and Notch signalling are critical regulators of stem cell fate.

Wnt signaling regulates Snai1 expression and cellular localization in the mouse intestinal epithelial stem cell niche.

Snail genes are transcriptional repressors well known to play important roles in epithelial to mesenchymal transitions during both embryogenesis and cancer metastasis. Although they are generally regarded as markers of mesenchymal cells, Snail genes have also recently been implicated in regulating stem cell populations in both Drosophila and vertebrates. In this study we investigate Snai1, a member of the mouse Snail family, in the intestinal stem cell niche and examine the relationship between canonical Wnt signaling, a key regulatory pathway of intestinal stem cells, and expression and cellular localization of Snai1.

Xenopus Dead end mRNA is a localized maternal determinant that serves a conserved function in germ cell development.

Germ plasm formation is considered to define the first step in germ cell development. Xenopus Dead end represents a germ plasm specific transcript that is homologous to the previously characterized zebrafish dead end, which is required for germ cell migration and survival. XDead end mRNA localizes to the vegetal pole of Xenopus oocytes; in contrast to all other known germ plasm associated transcripts in Xenopus, XDead end is transported via the late transport pathway, suggesting a different mode of germ plasm restriction.

Evidence for overlapping, but not identical, protein machineries operating in vegetal RNA localization along early and late pathways in Xenopus oocytes.

RNAs that localize to the vegetal cortex of Xenopus oocytes are involved in early embryonic patterning and cell fate specification. Two mechanistically distinct pathways lead to RNA enrichment at the vegetal cortex: the early and the late. While several candidate proteins that seem to operate in the late localization pathway have been identified, proteins involved in the early pathway remain to be identified.

The alpha-helical D1 domain of the tobacco bZIP transcription factor BZI-1 interacts with the ankyrin-repeat protein ANK1 and is important for BZI-1 function, both in auxin signaling and pathogen response.

The tobacco (Nicotiana tabacum) bZIP transcription factor BZI-1 is involved in auxin-mediated growth responses and in establishing pathogen defenses. Transgenic plants expressing a dominant-negative BZI-1-DeltaN derivative, which lacks the N-terminal activation domain, showed altered vegetative growth. In particular auxin-induced rooting and formation of tobacco mosaic virus-induced hypersensitive response lesions are affected.