Viral infection disrupts intestinal homeostasis via Sting-dependent NF-κB signaling in Drosophila.

Host-microbe interactions influence intestinal stem cell (ISC) activity to modulate epithelial turnover and composition. Here, we investigated the functional impacts of viral infection on intestinal homeostasis and the mechanisms by which viral infection alters ISC activity. We report that Drosophila A virus (DAV) infection disrupts intestinal homeostasis in Drosophila by inducing sustained ISC proliferation, resulting in intestinal dysplasia, loss of gut barrier function, and reduced lifespan.

Applying mechanical forces on Drosophila tissues in vivo using the StretchCo, a 3D-printable device.

Applying mechanical forces to tissues helps to understand morphogenesis and homeostasis. Additionally, recording the dynamics of living tissues under mechanical constraints is needed to explore tissue biomechanics. Here, we present a protocol to 3D-print a StretchCo device and use it to apply uniaxial mechanical stress on the Drosophila pupal dorsal thorax epithelium.

Chromatin state transitions in the Drosophila intestinal lineage identify principles of cell-type specification.

Tissue homeostasis relies on rewiring of stem cell transcriptional programs into those of differentiated cells. Here, we investigate changes in chromatin occurring in a bipotent adult stem cells. Combining mapping of chromatin-associated factors with statistical modeling, we identify genome-wide transitions during differentiation in the adult Drosophila intestinal stem cell (ISC) lineage.

Molecular underpinnings and environmental drivers of loss of heterozygosity in Drosophila intestinal stem cells.

During development and aging, genome mutation leading to loss of heterozygosity (LOH) can uncover recessive phenotypes within tissue compartments. This phenomenon occurs in normal human tissues and is prevalent in pathological genetic conditions and cancers. While studies in yeast have defined DNA repair mechanisms that can promote LOH, the predominant pathways and environmental triggers in somatic tissues of multicellular organisms are not well understood.

Illuminati: a form of gene expression plasticity in Drosophila neural stem cells.

While testing for genome instability in Drosophila as reported by unscheduled upregulation of UAS-GFP in cells that co-express GAL80 and GAL4, we noticed that, as expected, background levels were low in most developing tissues. However, GFP-positive clones were frequent in the larval brain. Most of these clones originated from central brain neural stem cells.

Stem cells: Mitochondrial biogenesis links growth and EGFR signaling.

Epidermal growth factor receptor signaling is central to cell proliferation, growth, and survival and is often deregulated in cancers. A new study links downstream effectors of this receptor to stem cell growth via mitochondrial biogenesis and metabolic reprogramming.

An amuse-bouche of stem cell regulation: Underlying principles and mechanisms from adult Drosophila intestinal stem cells.

Stem cells have essential functions in the development and maintenance of our organs. Improper regulation of adult stem cells and tissue homeostasis can result in cancers and age-dependent decline. Therefore, understanding how tissue-specific stem cells can accurately renew tissues is an important aim of regenerative medicine.

Evolution and genomic signatures of spontaneous somatic mutation in intestinal stem cells.

Spontaneous mutations can alter tissue dynamics and lead to cancer initiation. Although large-scale sequencing projects have illuminated processes that influence somatic mutation and subsequent tumor evolution, the mutational dynamics operating in the very early stages of cancer development are currently not well understood. To explore mutational processes in the early stages of cancer evolution, we exploited neoplasia arising spontaneously in the intestine.

Unraveling the features of somatic transposition in the Drosophila intestine.

Transposable elements (TEs) play a significant role in evolution, contributing to genetic variation. However, TE mobilization in somatic cells is not well understood. Here, we address the prevalence of transposition in a somatic tissue, exploiting the Drosophila midgut as a model.

Stem Cell DNA Damage and Genome Mutation in the Context of Aging and Cancer Initiation.

Adult stem cells fuel tissue homeostasis and regeneration through their unique ability to self-renew and differentiate into specialized cells. Thus, their DNA provides instructions that impact the tissue as a whole. Since DNA is not an inert molecule, but rather dynamic, interacting with a myriad of chemical and physical factors, it encounters damage from both endogenous and exogenous sources.

Stem Cell Proliferation Is Kept in Check by the Chromatin Regulators Kismet/CHD7/CHD8 and Trr/MLL3/4.

Chromatin remodeling accompanies differentiation, however, its role in self-renewal is less well understood. We report that in Drosophila, the chromatin remodeler Kismet/CHD7/CHD8 limits intestinal stem cell (ISC) number and proliferation without affecting differentiation. Stem-cell-specific whole-genome profiling of Kismet revealed its enrichment at transcriptionally active regions bound by RNA polymerase II and Brahma, its recruitment to the transcription start site of activated genes and developmental enhancers and its depletion from regions bound by Polycomb, Histone H1, and heterochromatin Protein 1.

Spen limits intestinal stem cell self-renewal.

Precise regulation of stem cell self-renewal and differentiation properties is essential for tissue homeostasis. Using the adult Drosophila intestine to study molecular mechanisms controlling stem cell properties, we identify the gene split-ends (spen) in a genetic screen as a novel regulator of intestinal stem cell fate (ISC). Spen family genes encode conserved RNA recognition motif-containing proteins that are reported to have roles in RNA splicing and transcriptional regulation.

Tissue homeostasis and aging: new insight from the fly intestine.

Adult somatic stem cells facilitate tissue homeostasis throughout the life of the organism. The mechanisms controlling stem cell activity are under intense scrutiny, with the aims of elucidating how they mediate tissue homeostasis, contribute to age-related decline of adult tissues, and promote tumorigenesis. Recently, the use of model systems such as the Drosophila intestine has enriched our understanding of how stem cells integrate local and systemic signals to maintain tissue and organs function in physiological conditions of homeostasis or after damage.

Somatic recombination in adult tissues: What is there to learn?

Somatic recombination is essential to protect genomes of somatic cells from DNA damage but it also has important clinical implications, as it is a driving force of tumorigenesis leading to inactivation of tumor suppressor genes. Despite this importance, our knowledge about somatic recombination in adult tissues remains very limited. Our recent work, using the Drosophila adult midgut has demonstrated that spontaneous events of mitotic recombination accumulate in aging adult intestinal stem cells and result in frequent loss of heterozygosity (LOH).

Frequent Somatic Mutation in Adult Intestinal Stem Cells Drives Neoplasia and Genetic Mosaicism during Aging.

Adult stem cells may acquire mutations that modify cellular behavior, leading to functional declines in homeostasis or providing a competitive advantage resulting in premalignancy. However, the frequency, phenotypic impact, and mechanisms underlying spontaneous mutagenesis during aging are unclear. Here, we report two mechanisms of genome instability in adult Drosophila intestinal stem cells (ISCs) that cause phenotypic alterations in the aging intestine.

Aneuploidy causes premature differentiation of neural and intestinal stem cells.

Aneuploidy is associated with a variety of diseases such as cancer and microcephaly. Although many studies have addressed the consequences of a non-euploid genome in cells, little is known about their overall consequences in tissue and organism development. Here we use two different mutant conditions to address the consequences of aneuploidy during tissue development and homeostasis in Drosophila.

Aurora B and cyclin B have opposite effects on the timing of cytokinesis abscission in Drosophila germ cells and in vertebrate somatic cells.

Abscission is the last step of cytokinesis that physically separates the cytoplasm of sister cells. As the final stage of cell division, abscission is poorly characterized during animal development. Here, we show that Aurora B and Survivin regulate the number of germ cells in each Drosophila egg chamber by inhibiting abscission during differentiation.

[The Drosophila midgut as a model to study adult stem cells].

Constant renewal of cells occurs in most tissues throughout the adult lifetime and is insured by the activity of resident stem cells. Recent work has demonstrated the presence of adult stem cells in the Drosophila intestine and consequently, the Drosophila intestine has become a powerful model to understand adult stem cells in vivo. In this review, we summarize our current understanding of the mechanisms controlling cell fate decisions of the intestinal stem cells with a particular focus on the role of the Notch pathway in this process.

Sending the right signal: Notch and stem cells.

Background: Notch signaling plays a critical role in multiple developmental programs and not surprisingly, the Notch pathway has also been implicated in the regulation of many adult stem cells, such as those in the intestine, skin, lungs, hematopoietic system, and muscle.

Scope Of Review: In this review, we will first describe molecular mechanisms of Notch component modulation including recent advances in this field and introduce the fundamental principles of Notch signaling controlling cell fate decisions. We will then illustrate its important and varied functions in major stem cell model systems including: Drosophila and mammalian intestinal stem cells and mammalian skin, lung, hematopoietic and muscle stem cells.

Drosophila midgut homeostasis involves neutral competition between symmetrically dividing intestinal stem cells.

The Drosophila adult posterior midgut has been identified as a powerful system in which to study mechanisms that control intestinal maintenance, in normal conditions as well as during injury or infection. Early work on this system has established a model of tissue turnover based on the asymmetric division of intestinal stem cells. From the quantitative analysis of clonal fate data, we show that tissue turnover involves the neutral competition of symmetrically dividing stem cells.

Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine.

Tight regulation of self-renewal and differentiation of adult stem cells ensures that tissues are properly maintained. In the Drosophila intestine, both commitment, i.e.

Notch signaling in intestinal homeostasis across species: the cases of Drosophila, Zebrafish and the mouse.

Notch signaling has been recently shown to have a fundamental role in stem cell maintenance and control of proper homeostasis in the intestine of different species. Here, we briefly review the current literature on Notch signals in the intestine of Drosophila, Zebrafish and the mouse, and try to highlight conserved and divergent Notch functions across species. Notch signals show a remarkably conserved role in skewing cell fate choices in intestinal lineages throughout evolution.