Regulation of the Intestinal Stem Cell Pool and Proliferation in .

Understanding the regulation of somatic stem cells, both during homeostasis and in response to environmental challenges like injury, infection, chemical exposure, and nutritional changes, is critical because their dysregulation can result in tissue degeneration or tumorigenesis. The use of models such as the and mammalian adult intestines offers valuable insights into tissue homeostasis and regeneration, advancing our knowledge of stem cell biology and cancer development. This review highlights significant findings from recent studies, unveiling the molecular mechanisms that govern self-renewal, proliferation, differentiation, and regeneration of intestinal stem cells (ISCs).

Numb provides a fail-safe mechanism for intestinal stem cell self-renewal in adult midgut.

Stem cell self-renewal often relies on asymmetric fate determination governed by niche signals and/or cell-intrinsic factors but how these regulatory mechanisms cooperate to promote asymmetric fate decision remains poorly understood. In adult midgut, asymmetric Notch (N) signaling inhibits intestinal stem cell (ISC) self-renewal by promoting ISC differentiation into enteroblast (EB). We have previously showed that epithelium-derived BMP promotes ISC self-renewal by antagonizing N pathway activity (Tian and Jiang, 2014).

Topoisomerase I is an evolutionarily conserved key regulator for satellite DNA transcription.

RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation.

EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity.

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors.

Damage-induced regeneration of the intestinal stem cell pool through enteroblast mitosis in the Drosophila midgut.

Many adult tissues and organs including the intestine rely on resident stem cells to maintain homeostasis and regeneration. In mammals, the progenies of intestinal stem cells (ISCs) can dedifferentiate to generate ISCs upon ablation of resident stem cells. However, whether and how mature tissue cells generate ISCs under physiological conditions remains unknown.

Tumor models in various Drosophila tissues.

The development of cancer is a complex multistage process. Over the past few decades, the model organism Drosophila melanogaster has been crucial in identifying cancer-related genes and pathways and elucidating mechanisms underlying growth regulation in development. Investigations using Drosophila has yielded new insights into the molecular mechanisms involved in tumor initiation and progression.

Gilgamesh (Gish)/CK1γ regulates tissue homeostasis and aging in adult Drosophila midgut.

Adult tissues and organs rely on resident stem cells to generate new cells that replenish damaged cells. To maintain homeostasis, stem cell activity needs to be tightly controlled throughout the adult life. Here, we show that the membrane-associated kinase Gilgamesh (Gish)/CK1γ maintains Drosophila adult midgut homeostasis by restricting JNK pathway activity and that Gish is essential for intestinal stem cell (ISC) maintenance under stress conditions.

Dual role of BMP signaling in the regulation of Drosophila intestinal stem cell self-renewal.

Many adult organs including Drosophila adult midguts rely on resident stem cells to replenish damaged cells during tissue homeostasis and regeneration. Previous studies have shown that, upon injury, intestinal stem cells (ISCs) in the midguts can increase proliferation and lineage differentiation to meet the demand for tissue repair. Our recent study has demonstrated that, in response to certain injury, midguts can expand ISC population size as an additional regenerative mechanism.

Injury-stimulated and self-restrained BMP signaling dynamically regulates stem cell pool size during midgut regeneration.

Many adult organs rely on resident stem cells to maintain homeostasis. Upon injury, stem cells increase proliferation, followed by lineage differentiation to replenish damaged cells. Whether stem cells also change division mode to transiently increase their population size as part of a regenerative program and, if so, what the underlying mechanism is have remained largely unexplored.

Intestinal stem cell response to injury: lessons from Drosophila.

Many adult tissues and organs are maintained by resident stem cells that are activated in response to injury but the mechanisms that regulate stem cell activity during regeneration are still poorly understood. An emerging system to study such problem is the Drosophila adult midgut. Recent studies have identified both intrinsic factors and extrinsic niche signals that control the proliferation, self-renewal, and lineage differentiation of Drosophila adult intestinal stem cells (ISCs).

Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells.

Many adult tissues are maintained by resident stem cells that elevate their proliferation in response to injury. The regulatory mechanisms underlying regenerative proliferation are still poorly understood. Here we show that injury induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem cell (ISC) proliferation in Drosophila melanogaster adult midgut.

Intestinal epithelium-derived BMP controls stem cell self-renewal in Drosophila adult midgut.

Stem cells are maintained in a specialized microenvironment called niche but the nature of stem cell niche remains poorly defined in many systems. Here we demonstrate that intestinal epithelium-derived BMP serves as a niche signal for intestinal stem cell (ISC) self-renewal in Drosophila adult midgut. We find that BMP signaling is asymmetric between ISC and its differentiated daughter cell.

Efficient EGFR signaling and dorsal-ventral axis patterning requires syntaxin dependent Gurken trafficking.

Vesicle trafficking plays a crucial role in the establishment of cell polarity in various cellular contexts, including axis-pattern formation in the developing egg chamber of Drosophila. The EGFR ligand, Gurken (Grk), is first localized at the posterior of young oocytes for anterior-posterior axis formation and later in the dorsal anterior region for induction of the dorsal-ventral (DV) axis, but regulation of Grk localization by membrane trafficking in the oocyte remains poorly understood. Here, we report that Syntaxin 1A (Syx1A) is required for efficient trafficking of Grk protein for DV patterning.

The cell adhesion molecule echinoid functions as a tumor suppressor and upstream regulator of the Hippo signaling pathway.

The Hippo (Hpo) signaling pathway controls tissue growth and organ size in species ranging from Drosophila to mammals and is deregulated in a wide range of human cancers. The core pathway consists of the Hpo/Warts (Wts) kinase cassette that phosphorylates and inactivates the transcriptional coactivator Yorkie (Yki). Here, we report that Echinoid (Ed), an immunoglobulin domain-containing cell adhesion molecule, acts as an upstream regulator of the Hpo pathway.

Wheat WRKY genes TaWRKY2 and TaWRKY19 regulate abiotic stress tolerance in transgenic Arabidopsis plants.

WRKY-type transcription factors are involved in multiple aspects of plant growth, development and stress response. WRKY genes have been found to be responsive to abiotic stresses; however, their roles in abiotic stress tolerance are largely unknown especially in crops. Here, we identified stress-responsive WRKY genes from wheat (Triticum aestivum L.

Soybean NAC transcription factors promote abiotic stress tolerance and lateral root formation in transgenic plants.

NAC transcription factors play important roles in plant growth, development and stress responses. Previously, we identified multiple NAC genes in soybean (Glycine max). Here, we identify the roles of two genes, GmNAC11 and GmNAC20, in stress responses and other processes.

Involvement of Lgl and Mahjong/VprBP in cell competition.

During the initial stages of carcinogenesis, transformation events occur in a single cell within an epithelial monolayer. However, it remains unknown what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila, it has been recently shown that normal and transformed cells compete with each other for survival in an epithelial tissue; however the molecular mechanisms whereby "loser cells" undergo apoptosis are not clearly understood.

Soybean Trihelix transcription factors GmGT-2A and GmGT-2B improve plant tolerance to abiotic stresses in transgenic Arabidopsis.

Background: Trihelix transcription factors play important roles in light-regulated responses and other developmental processes. However, their functions in abiotic stress response are largely unclear. In this study, we identified two trihelix transcription factor genes GmGT-2A and GmGT-2B from soybean and further characterized their roles in abiotic stress tolerance.

Par-1 and Tau regulate the anterior-posterior gradient of microtubules in Drosophila oocytes.

The formation of an anterior-posterior (AP) gradient of microtubules in Drosophila oocytes is essential for specification of the AP axis. Proper microtubule organization in the oocyte requires the function of serine/threonine kinase Par-1. The N1S isoform of Par-1 is enriched at the posterior cortex of the oocyte from stage 7 of oogenesis.

Soybean WRKY-type transcription factor genes, GmWRKY13, GmWRKY21, and GmWRKY54, confer differential tolerance to abiotic stresses in transgenic Arabidopsis plants.

WRKY-type transcription factors have multiple roles in the plant defence response and developmental processes. Their roles in the abiotic stress response remain obscure. In this study, 64 GmWRKY genes from soybean were identified, and were found to be differentially expressed under abiotic stresses.

Soybean GmbZIP44, GmbZIP62 and GmbZIP78 genes function as negative regulator of ABA signaling and confer salt and freezing tolerance in transgenic Arabidopsis.

From soybean plant, 131 bZIP genes were identified and named as GmbZIPs. The GmbZIPs can be classified into ten groups and more than one third of these GmbZIPs are responsive to at least one of the four treatments including ABA, salt, drought and cold stresses. Previous studies have shown that group A bZIP proteins are involved in ABA and stress signaling.

Lgl and its phosphorylation by aPKC regulate oocyte polarity formation in Drosophila.

Specification of the anteroposterior (AP) axis in Drosophila oocytes requires proper organization of the microtubule and actin cytoskeleton. The establishment and regulation of cytoskeletal polarity remain poorly understood, however. Here, we show important roles for the tumor suppressor Lethal (2) giant larvae (Lgl) and atypical protein kinase C (aPKC) in regulating microtubule polarity and setting up the AP axis of the oocyte.

The soybean Dof-type transcription factor genes, GmDof4 and GmDof11, enhance lipid content in the seeds of transgenic Arabidopsis plants.

Soybean is one of the most important leguminous seed crops among the oil crops. Although the pathways for lipid biosynthesis have been identified, the factors that regulate the biosynthetic pathways at the transcriptional level are largely unknown. Here, we report our findings on the involvement of soybean Dof-type transcription factor genes in the regulation of the lipid content in soybean seeds.