LncRNA CR43282-CR46040 Regulates The Proliferation Of Intestinal Stem Cells In Drosophila

Tissue homeostasis is a dynamic process that requires the production of new cells to replenish those that are aging and damaged,and to maintain a good balance.Stem cells play a key role in this process.Intestinal is one of the tissues with the fastest metabolism.When the intestinal is damaged,intestinal stem cells can continue to proliferate to renew damaged epithelial cells.Therefore,intestinal stem cells play a very important role in maintaining intestinal homeostasis and intestinal barrier function.Drosophila digestive tract epithelium is a pseudo-lamellar monolayer that is morphologically differentiated into different regions.The midgut is the most representative,including different subregions and gene expression profiles based on different morphological and histological characteristics.Intestinal stem cells(ISCs)show the highest proliferation rate in the midgut(PMG),express Notch ligand Delta(D1),and continue to produce doubleeffective intestinal cells(EBs).Although both ISCs and EBs express the transcription factor escargot(esg),activation of the Notch receptor in EB results in inhibition of Su(H)activation and differentiation into resorbable intestinal cells(EC)that express the POU domain transcription factor Pdm1.Importantly,a portion of Su(H)+ EB differentiates into type II enteroendocrine cells(EE)that express Prospero and specific neuropeptides.Under physiological and stress conditions,ISC division and differentiation are controlled by several pathways including JNK,Egfr / Ras / MAPK,Notch,Wnt,JAK-STAT and m TOR.The m TOR pathway is a well-known master regulator of autophagy,but its downstream effectors are unknown in the context of ISC division / differentiation.The structure and cell composition of the drosophila intestinal tract is similar to that of mammals.The midgut is the mammalian small intestine,which digests food and absorbs nutrients,and the hindgut is the mammalian large intestine.Mammalian intestinal stem cells divide and differentiate longitudinally from the crypts to the lumen near the basement membrane,and the ISC divides to produce the TA cell,followed by the differentiation of EC?EE and paneth cells,with a layer of mucosa near the lumen.The composition of the intestinal epidermal cells of the fruit fly is similar to that of the fruit fly.Intestinal stem cells are also close to the basement membrane and divide to produce EB cells,which then differentiate into intestinal epithelial cells(EC).They have bristles and polyploid nuclei,absorb nutrients,intestinal endocrine cells(EE)and secrete hormones.The drosophila gut has become a classic model for studying intestinal stem cells because of its structural similarities and genetic predominance in mammals.In recent years,lnc RNA has become an important regulator of cell processes in normal development and disease.They generally exhibit tissue and cell type-specific expression patterns and are potentially involved in biological processes such as cell fate designation and differentiation.Their role is usually in the nucleus,in the process of transcriptional responses and regulating the structure and function of chromatin.At present,to our knowledge,there are no reports of lnc RNAs specific and essential for Drosophila ISC.We wonder whether lnc RNA is also involved in regulating the proliferation and differentiation of intestinal stem cells.We found that the number of intestinal stem cells in knockout Drosophila CR43282-CR46040 knockout Drosophila was reduced compared to the control by DSS feeding on Drosophila screening,indicating that CR43282-CR46040 affects the proliferation of intestinal stem cells under the conditions of intestinal regeneration of Drosophila.After that,we found that the decrease in the number of CR43282-CR46040 knockout Drosophila strain ISC / EB cells was caused by the decrease of ISC proliferation by PH3 immunofluorescent antibody staining,indicating that CR43282-CR46040 participates in the proliferation of ISCs during intestinal regeneration.At the same time,we used complementary experiments to confirm that the absence of CR43282-CR46040 caused this phenomenon.We have confirmed through the MARCM cloning experiment that CR43282-CR46040 is involved in the proliferation of ISCs after injury.Then we examined the activation of related pathways under injury conditions,and we found that CR43282-CR46040 did indeed cause a significant reduction in JAK-STAT pathway activation.Interestingly,our research found that CR43282-CR46040 does not participate in the differentiation process of ISCs.Lnc RNA has not yet been reported on the regulation of intestinal stem cells,and this study provides further insights into the regulatory mechanism of intestinal stem cell proliferation and differentiation.