bioRxiv - Developmental Biology最新文献_第6页

Proliferation and differentiation of intestinal stem cells depends on the zinc finger transcription factor BCL11/Chronophage 肠干细胞的增殖和分化取决于锌指转录因子 BCL11/Chronophage

bioRxiv - Developmental Biology Pub Date : 2024-09-09 DOI: 10.1101/2024.09.08.611891

Siamak Redhai, Nick Hirschmueller, Tianyu Wang, Shivohum Bahuguna, Svenja Leible, Stefan Peidli, Erica Valentini, Sviatoslav Kharuk, Michaela Holzem, Lea Braeckow, Fillip Port, David Ibberson, Wolfgang Huber, Michael Boutros

{"title":"Proliferation and differentiation of intestinal stem cells depends on the zinc finger transcription factor BCL11/Chronophage","authors":"Siamak Redhai, Nick Hirschmueller, Tianyu Wang, Shivohum Bahuguna, Svenja Leible, Stefan Peidli, Erica Valentini, Sviatoslav Kharuk, Michaela Holzem, Lea Braeckow, Fillip Port, David Ibberson, Wolfgang Huber, Michael Boutros","doi":"10.1101/2024.09.08.611891","DOIUrl":"https://doi.org/10.1101/2024.09.08.611891","url":null,"abstract":"The molecular programs that drive proliferation and differentiation of intestinal stem cells (ISCs) are essential for organismal fitness. Notch signalling regulates the binary fate decision of ISCs, favouring enterocyte commitment when Notch activity is high and enteroendocrine cell (EE) fate when activity is low. However, the gene regulatory mechanisms that underlie this process on an organ scale remain poorly understood. Here, we find that the expression of the C2H2-type zinc-finger transcription factor Chronophage (Cph), homologous to mammalian BCL11, increases specifically along the ISC-to-EE lineage when Notch is inactivated. We show that the expression of Cph is regulated by the Achaete-Scute Complex (AS-C) gene, scute, which directly binds to multiple sites within the Cph locus to promote its expression. Our genetic and single-cell RNA sequencing experiments demonstrate that Cph maintains the ISC and EE populations and is necessary to remodel the transcriptome of progenitor cells with low Notch activity. By identifying and functionally validating Cph target genes, we uncover a novel role for sugar free frosting (sff) in directing proliferative and lineage commitment steps of ISCs. Our results shed light on the mechanisms by which Cph sustains intestinal epithelial homeostasis and could represent a conserved strategy for balancing proliferation and differentiation in different tissues and species.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the Cell-Specific Transcript Heterogeneity and Alternative Splicing during the Early Embryonic Development of Zebrafish 解密斑马鱼早期胚胎发育过程中的细胞特异性转录本异质性和替代剪接

bioRxiv - Developmental Biology Pub Date : 2024-09-09 DOI: 10.1101/2024.09.08.611790

Xiumei Lin, Xue Wang, Chang Liu, Chuanyu Liu, Tao Zeng, Ziqi Yuan, Meidi Hu, Rong Xiang, Kaichen Zhao, Jie Zhou, Shichen Yang, Yang Wang, Kaifeng Meng, Hui Wang, Guangli He, Rui Zhao, Jiaheng Liu, Yunqi Huang, Jingfang Pan, Jialu Wang, Junyi Chen, Fei Guo, Yuliang Dong, Xun Xu, Daji Luo, Ying Gu, Longqi Liu, Zhiqiang Dong, Liang Chen

{"title":"Deciphering the Cell-Specific Transcript Heterogeneity and Alternative Splicing during the Early Embryonic Development of Zebrafish","authors":"Xiumei Lin, Xue Wang, Chang Liu, Chuanyu Liu, Tao Zeng, Ziqi Yuan, Meidi Hu, Rong Xiang, Kaichen Zhao, Jie Zhou, Shichen Yang, Yang Wang, Kaifeng Meng, Hui Wang, Guangli He, Rui Zhao, Jiaheng Liu, Yunqi Huang, Jingfang Pan, Jialu Wang, Junyi Chen, Fei Guo, Yuliang Dong, Xun Xu, Daji Luo, Ying Gu, Longqi Liu, Zhiqiang Dong, Liang Chen","doi":"10.1101/2024.09.08.611790","DOIUrl":"https://doi.org/10.1101/2024.09.08.611790","url":null,"abstract":"Cell fate determination during early embryonic development is a complex process modulated by gene expression. The intricate interplay of transcriptional and post-transcriptional regulation is integral to the developmental trajectory of embryogenesis, yet how RNA processing may contribute to early development programming is largely elusive. Leveraging recent technological advances in single-molecule nanopore sequencing, we developed a single-cell long-read transcriptome sequencing technology, allowing a clear view of transcript diversity during zebrafish embryogenesis, particularly spanning the periods of pre- and post-zygotic genome activation (ZGA). A closer examination of the dynamic transcript usage and potential alternative splicing revealed that abundant stage-specific transcripts with differential coding potentials are involved in distinct biological functions. Specifically, we identified two cell populations at the onset of ZGA based on isoform diversity instead of gene profiling, which followed divergent developmental trajectories toward the ectoderm and the presumptive ectoderm. These two populations of cells were characterized by divergent splicing regulations linked to differential RNA-binding proteins, including SNRPA and SFPQ. Altogether, using the single-cell long-read transcriptome sequencing strategy, our work has revealed the cell-specific transcriptome dynamics contributing to the cell fate determination during embryogenesis.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSF pressure in fetal mice in utero: External factors pressurize the intraventricular space 宫内胎鼠的脑脊液压力：外部因素给脑室内空间加压

bioRxiv - Developmental Biology Pub Date : 2024-09-08 DOI: 10.1101/2024.09.08.611845

Koichiro Tsujikawa, Reina Muramatsu, Takaki Miyata

{"title":"CSF pressure in fetal mice in utero: External factors pressurize the intraventricular space","authors":"Koichiro Tsujikawa, Reina Muramatsu, Takaki Miyata","doi":"10.1101/2024.09.08.611845","DOIUrl":"https://doi.org/10.1101/2024.09.08.611845","url":null,"abstract":"Previous experiments inducing leakage of embryonic cerebrospinal fluid (CSF) suggest the necessity of intraventricular CSF pressure (PCSF) for brain morphogenesis. Nevertheless, how embryonic PCSF occurs is unclear, especially in utero. Using a Landis water manometer, we measured PCSF in fetal mice isolated from the amniotic cavity (PCSF-ISO). At embryonic day (E) 13, PCSF-ISO was 82.7 Pa. Intraventricular injections of ≥2 μl of saline elevated PCSF-ISO by ~30%. Intraventricularly injecting inhibitors of CSF secretion decreased PCSF-ISO by ~30%. Shh-mediated cerebral-wall expansion and the resulting ventricular narrowing did not significantly increase PCSF-ISO. Removal of the brain-surrounding contractile tissues decreased PCSF-ISO by 80-90%. The intraamniotic pressure measured in utero (PAF-IU) was 1030.7 Pa. Our direct measurement revealed that the PCSF in utero (PCSF-IU) was 1076.4 Pa, confirming the susceptibility of PCSF to external factors. Subsequent PCSF measurements under hydrostatic pressure loading suggested that PCSF-IU = PCSF-ISO + PAF-IU, a relationship further used to estimate PCSF-IU at other ages when direct measurement was not possible. The estimated PCSF-IU decreased almost constantly from E10 to E16 (2000 → 500 Pa).","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mouse nephron formation is impaired by moderate-dose arsenical exposure 中剂量砷暴露会损害小鼠肾小球的形成

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.06.611740

Carlos A I Alonso, Jenna Haverfield, Gabriela Regalado, Sihem Sellami, Natascha Gagnon, Ajay Rajaram, Pierre O Fiset, Aimee K Ryan, Koren K Mann, Indra R Gupta

{"title":"Mouse nephron formation is impaired by moderate-dose arsenical exposure","authors":"Carlos A I Alonso, Jenna Haverfield, Gabriela Regalado, Sihem Sellami, Natascha Gagnon, Ajay Rajaram, Pierre O Fiset, Aimee K Ryan, Koren K Mann, Indra R Gupta","doi":"10.1101/2024.09.06.611740","DOIUrl":"https://doi.org/10.1101/2024.09.06.611740","url":null,"abstract":"Background: Arsenic is a naturally occurring toxicant and industrial byproduct with significant health risks. Globally, millions of people are exposed to arsenic concentrations that exceed the World Health Organization's recommended limit of 10 μg/L. Chronic arsenic exposure is linked to an increased risk of chronic kidney disease (CKD); however, the effects of arsenic exposure on kidney development remain unclear. Eukaryotes methylate inorganic arsenic (iAsIII) using the enzyme arsenic 3 methyltransferase (As3mt), that converts it to methylated intermediates, mono and dimethyl arsonous acid (MMAIII and DMAIII), and mono and dimethyl arsonic acid (MMAV and DMAV). We hypothesized that arsenicals exposure during mouse kidney development impairs nephron formation. Methods: Cultured mouse embryonic kidney explants were treated with inorganic arsenite (iAsIII), MMAIII, MMAV, and DMAV. Female mice harboring a humanized version of AS3MT and wild-type mice with murine As3mt were exposed to iAsIII throughout gestation and weaning and their offspring were analyzed for kidney defects. Results: Inorganic arsenic, iAsIII (200 μ/L), inhibited ureteric bud branching morphogenesis and growth of mouse kidneys at embryonic day 11.5 (E11.5) and E12.5, but not at E13.5. MMAIII, but not MMAV or DMAV, impaired ureteric bud branching and kidney explant growth. Additionally, iAsIII exposure increased apoptosis in the metanephric mesenchyme of E11.5 explants and decreased Gdnf transcription, which may explain the impairment in ureteric bud branching. Humanized mouse pups exposed to 200 μ/L iAsIII in utero, showed a 20% reduction in kidney weight normalized to body weight and a 28% reduction in nephron number, compared to kidneys of wild-type mice. Conclusion: Exposure to arsenicals during embryonic development impairs ureteric bud branching morphogenesis and decreases nephron endowment, which may predispose to CKD in adulthood.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ciliary marginal zone of the developing human retina maintains retinal progenitor cells until late gestational stages 发育中的人类视网膜睫状边缘区可维持视网膜祖细胞直至妊娠晚期

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.03.611053

Kiara C. Eldred, Sierra J Edgerton, Isabel Ortuno-Lizaran, Juliette Wohlschlegel, Stephanie M Sherman, Sidnee Petter, Gracious Wyatt-Draher, Dawn Hoffer, Ian Glass, Anna C La Torre, Thomas A Reh

{"title":"Ciliary marginal zone of the developing human retina maintains retinal progenitor cells until late gestational stages","authors":"Kiara C. Eldred, Sierra J Edgerton, Isabel Ortuno-Lizaran, Juliette Wohlschlegel, Stephanie M Sherman, Sidnee Petter, Gracious Wyatt-Draher, Dawn Hoffer, Ian Glass, Anna C La Torre, Thomas A Reh","doi":"10.1101/2024.09.03.611053","DOIUrl":"https://doi.org/10.1101/2024.09.03.611053","url":null,"abstract":"Non-mammalian vertebrates maintain a proliferative stem cell population at the far periphery of their retina called the ciliary marginal zone (CMZ), which gives rise to all retinal cell types and contributes to retinal regeneration upon injury. Humans do not maintain a proliferative CMZ into adulthood; however, it is not known how long in development this region continues to generate new neurons. Here, we identify a population of cells in the far peripheral retina of the fetal human that continues to proliferate long after the rest of the retina is quiescent. Single cell RNA-sequencing and EdU tracing at late time points in development reveal that this region has features of the non-mammalian CMZ, including the capacity to produce both early and late born cell types at late developmental stages, and a longer cell cycle than more centrally located retinal progenitor cells (RPCs). Moreover, while more central RPCs exit the cell cycle with the addition of a TGFB-inhibitor, we show that early RPCs within the CMZ do not. These findings define the late stages of neurogenesis in human retinal development, and present a unique model system to study the fetal CMZ in humans.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Planar cell polarity coordination in a cnidarian embryo provides clues to animal body axis evolution 刺胞动物胚胎中的平面细胞极性协调为动物体轴进化提供了线索

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.05.609312

Julie Uveira, Antoine Donati, Marvin Léria, Marion Lechable, François Lahaye, Christine Vesque, Evelyn Houliston, Tsuyoshi Momose

{"title":"Planar cell polarity coordination in a cnidarian embryo provides clues to animal body axis evolution","authors":"Julie Uveira, Antoine Donati, Marvin Léria, Marion Lechable, François Lahaye, Christine Vesque, Evelyn Houliston, Tsuyoshi Momose","doi":"10.1101/2024.09.05.609312","DOIUrl":"https://doi.org/10.1101/2024.09.05.609312","url":null,"abstract":"Body axis specification is a crucial event in animal embryogenesis, and was an essential evolutionary innovation for founding the animal kingdom. It involves two distinct components that coordinate to establish the spatial organisation of the embryo: initiation of cascades of regionalised gene expression and orientation of morphogenetic processes such as body elongation. Intense interest in the first component has revealed Wnt/β-catenin signalling as ancestrally responsible for initiating regional gene expression, but the evolutionary origin of oriented morphogenesis has received little attention. Here, by addressing the cell and morphological basis of body axis development in embryos of the cnidarian Clytia hemisphaerica, we have uncovered a simple and likely ancestral coordination mechanism between Wnt/β-catenin signalling and directed morphogenesis. We show that the ligand Wnt3, known to initiate oral gene expression via localised Wnt/β-catenin pathway activation, also has a key β-catenin-independent role in globally orienting planar cell polarity (PCP) to direct morphogenesis along the oral-aboral axis. This PCP orientation occurs in two distinct steps: local orientation by Wnt3 and global propagation by conserved core PCP protein interactions along the body axis. From these findings we propose novel scenarios for PCP-driven symmetry-breaking underlying the emergence of the animal body plan.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Drosophila myogenic inhibitor Him gene is essential for adult muscle function and muscle stem cell maintenance 果蝇肌生成抑制因子 Him 基因对成体肌肉功能和肌肉干细胞维持至关重要

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.06.611611

Robert Mitchell-Gee, Robert Hoff, Kumar Vishal, Daniel Hancock, Sam McKitrick, Cristina Newnes-Querejeta, TyAnna Lovato, Richard Cripps, Michael Taylor

{"title":"The Drosophila myogenic inhibitor Him gene is essential for adult muscle function and muscle stem cell maintenance","authors":"Robert Mitchell-Gee, Robert Hoff, Kumar Vishal, Daniel Hancock, Sam McKitrick, Cristina Newnes-Querejeta, TyAnna Lovato, Richard Cripps, Michael Taylor","doi":"10.1101/2024.09.06.611611","DOIUrl":"https://doi.org/10.1101/2024.09.06.611611","url":null,"abstract":"Vertebrate muscle fibres have a population of Muscle Stem Cells (MuSCs), or satellite cells, vital to muscle growth, homeostasis and repair. In Drosophila, adult MuSCs with similar characteristics have only recently been described. This has opened up the Drosophila system for analysing how MuSCs operate in muscle maintenance, repair and ageing. Here we show that the Him gene is expressed in the adult muscle progenitors (AMPs), or myoblasts, that make the adult Drosophila thoracic flight and jump muscles. Notably, we also show that Him is expressed in the flight muscle MuSCs identifying Him as only the second genetic marker of these insect MuSCs. We then explored Him function. Him mutants have disrupted organisation of the thoracic jump muscle, resulting in reduced jumping ability. Him mutants also have a reduced pool of the myoblasts that will develop into the flight muscles. In the flight muscles themselves, Him mutants have an age-dependent decrease in the number of MuSCs, indicating that Him is required for maintenance of the adult muscle stem cell population. Moreover, this decrease in MuSCs coincides with a functional effect: there is an age- dependent decline in flight ability. Overall, Him is a novel marker of the Drosophila adult MuSC, and is required during ageing both to maintain MuSC number and flight ability.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"264 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases 盐诱导激酶控制牙槽骨的发育、稳态和牙槽愈合

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.04.611228

Nicha Tokavanich, Byron Chan, Katelyn Strauss, Chris Castro, Yuki Arai, Mizuki Nagata, Marc Foretz, Daniel J Brooks, Noriaki Ono, Wanida Ono, Marc Wein

{"title":"Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases","authors":"Nicha Tokavanich, Byron Chan, Katelyn Strauss, Chris Castro, Yuki Arai, Mizuki Nagata, Marc Foretz, Daniel J Brooks, Noriaki Ono, Wanida Ono, Marc Wein","doi":"10.1101/2024.09.04.611228","DOIUrl":"https://doi.org/10.1101/2024.09.04.611228","url":null,"abstract":"Alveolar bone supports and anchors teeth. The parathyroid hormone-related protein (PTHrP) pathway plays a key role in alveolar bone biology. Salt inducible kinases (SIKs) are important downstream regulators of PTH/PTHrP signaling in the appendicular skeleton, where SIK inhibition increases bone formation and trabecular bone mass. However, the function of these kinases in alveolar bone remains unknown. Here, we report a critical role for SIK2/SIK3 in alveolar bone development, homeostasis, and socket healing after tooth extraction. Inducible SIK2/SIK3 deletion led to dramatic alveolar bone defects without changes in tooth eruption. Ablating these kinases impairs alveolar bone formation due to disrupted osteoblast maturation, a finding associated with ectopic periostin expression by fibrous cells in regions of absent alveolar bone at steady state and following molar extraction. Distinct phenotypic consequences of SIK2/SIK3 deletion in appendicular versus craniofacial bones prompted us to identify a specific transcriptomic signature in alveolar versus long bone osteoblasts. Thus, SIK2/SIK3 deletion illuminates a key role for these kinases in alveolar bone biology and highlights the emerging concept that different osteoblast subsets utilize unique genetic programs.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Pax transcription factor EGL-38 links EGFR signaling to assembly of a cell-type specific apical extracellular matrix in the Caenorhabditis elegans vulva Pax转录因子EGL-38将表皮生长因子受体信号转导与草履虫外阴部细胞类型特异性顶端细胞外基质的组装联系起来

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.04.611291

Helen Frances Schmidt, Chelsea B Darwin, Meera V Sundaram

{"title":"The Pax transcription factor EGL-38 links EGFR signaling to assembly of a cell-type specific apical extracellular matrix in the Caenorhabditis elegans vulva","authors":"Helen Frances Schmidt, Chelsea B Darwin, Meera V Sundaram","doi":"10.1101/2024.09.04.611291","DOIUrl":"https://doi.org/10.1101/2024.09.04.611291","url":null,"abstract":"The surface of epithelial tissues is covered by an apical extracellular matrix (aECM). The aECMs of different tissues have distinct compositions to serve distinct functions, yet how a particular cell type assembles the proper aECM is not well understood. We used the cell-type specific matrix of the C. elegans vulva to investigate the connection between cell identity and matrix assembly. The vulva is an epithelial tube composed of seven cell types descending from EGFR/Ras-dependent (1°) and Notch-dependent (2°) lineages. Vulva aECM contains multiple Zona Pellucida domain (ZP) proteins, which are a common component of aECMs across life. ZP proteins LET-653 and CUTL-18 assemble on 1° cell surfaces, while NOAH-1 assembles on a subset of 2° surfaces. All three ZP genes are broadly transcribed, indicating that cell-type specific ZP assembly must be determined by features of the destination cell surface. The paired box (Pax) transcription factor EGL-38 promotes assembly of 1°-matrix and prevents inappropriate assembly of 2° matrix, suggesting that EGL-38 promotes expression of one or more ZP matrix organizers. Our results connect the known signaling pathways and various downstream effectors to EGL-38/Pax expression and the ZP matrix component of vulva cell fate execution. We propose that dedicated transcriptional networks may contribute to cell-appropriate assembly of aECM in many epithelial organs.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis 分泌 GDF11 的细胞移植可有效改善老年性肺纤维化

bioRxiv - Developmental Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.06.611670

Andras Nagy, Li Guo, Pascal Duchesneau, Evan Sawula, Eric D Jong, Chengjin Li, Tom Waddell

{"title":"GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis","authors":"Andras Nagy, Li Guo, Pascal Duchesneau, Evan Sawula, Eric D Jong, Chengjin Li, Tom Waddell","doi":"10.1101/2024.09.06.611670","DOIUrl":"https://doi.org/10.1101/2024.09.06.611670","url":null,"abstract":"Here, we present a combination of cell and gene therapy that harnesses the regenerative properties of GDF11 in age-related pulmonary fibrosis. Our genome-edited FailSafeTM-GDF11 mouse ESC line provides controlled proliferation and efficient derivation to lung progenitors while inducibly expressing GDF11. When these cells were transplanted into bleomycin-injured aged mice, they acted as a source of reparative cells, restoring the damaged alveolar epithelium. Furthermore, the transplanted cells acted as an in situ factory, enabling the production of GDF11 in response to the inducer drug. This approach attenuated age-associated senescence and led to the successful resolution of fibrosis. Our study presents a promising method for treating pulmonary fibrosis. Additionally, this approach offers a versatile tool that can be expanded to incorporate other regenerative and anti-aging factors. This helps overcome limitations such as high production costs and a short half-life of therapeutic factors. One of the strengths of our system is its ability to allow precise regulation of factor-expression when needed to address specific aging phenotypes.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0