Pub Date : 2026-02-02DOI: 10.1186/s12860-026-00570-2
Lauren Cuoco, Shelbi E Gill, Luc Francois, Sarah Souders, Caroline DeMasi, Jeffrey R Moore, Frédéric J J Chain
Background: Huntingtin (HTT) is an important gene for cellular processes such as autophagy, and its loss leads to neurodegenerative disease phenotypes. In Dictyostelium discoideum, HTT-null (htt-) cells exhibit impaired basal autophagy and fail to develop in the presence of ammonium chloride.
Results: Here we conducted a mutagenesis screen on htt- cells to identify potential genetic suppressors of the htt- phenotype. A mutant strain was isolated that counteracts many of the hallmark defects engendered with htt loss. This mutant, htt-;supX, rescues the growth, cargo degradation defects, developmental timing, and autophagic flux of htt- cells under ammonium chloride stress, representing a partial rescue of the htt- phenotype. Whole-genome sequencing revealed four mutations in the mutant strain affecting genes involved in vesicle trafficking, signal transduction, metal ion regulation, and fatty acid elongation. Transcriptome sequencing further identified 208 differentially expressed genes in the mutant strain, including genes whose expression was returned to wild-type levels, suggesting a potential mechanism by which htt-;supX mediates phenotypic recovery. Among these, five genes have known autophagy-related functions and may be implicated in pathways such as Rab GTPase regulation and SNARE-mediated vesicle fusion.
Conclusions: Our study highlights the ability of second-site mutations to restore autophagic function in the absence of HTT and identifies candidate genes and pathways for further investigation into Huntington's Disease models and autophagy modulation.
{"title":"Genetic suppressor of autophagy defects in huntingtin null cells identified using a mutagenesis screen in Dictyostelium discoideum.","authors":"Lauren Cuoco, Shelbi E Gill, Luc Francois, Sarah Souders, Caroline DeMasi, Jeffrey R Moore, Frédéric J J Chain","doi":"10.1186/s12860-026-00570-2","DOIUrl":"https://doi.org/10.1186/s12860-026-00570-2","url":null,"abstract":"<p><strong>Background: </strong>Huntingtin (HTT) is an important gene for cellular processes such as autophagy, and its loss leads to neurodegenerative disease phenotypes. In Dictyostelium discoideum, HTT-null (htt-) cells exhibit impaired basal autophagy and fail to develop in the presence of ammonium chloride.</p><p><strong>Results: </strong>Here we conducted a mutagenesis screen on htt- cells to identify potential genetic suppressors of the htt- phenotype. A mutant strain was isolated that counteracts many of the hallmark defects engendered with htt loss. This mutant, htt-;supX, rescues the growth, cargo degradation defects, developmental timing, and autophagic flux of htt- cells under ammonium chloride stress, representing a partial rescue of the htt- phenotype. Whole-genome sequencing revealed four mutations in the mutant strain affecting genes involved in vesicle trafficking, signal transduction, metal ion regulation, and fatty acid elongation. Transcriptome sequencing further identified 208 differentially expressed genes in the mutant strain, including genes whose expression was returned to wild-type levels, suggesting a potential mechanism by which htt-;supX mediates phenotypic recovery. Among these, five genes have known autophagy-related functions and may be implicated in pathways such as Rab GTPase regulation and SNARE-mediated vesicle fusion.</p><p><strong>Conclusions: </strong>Our study highlights the ability of second-site mutations to restore autophagic function in the absence of HTT and identifies candidate genes and pathways for further investigation into Huntington's Disease models and autophagy modulation.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of irisin on inflammatory and apoptotic markers in the Caco-2 colon cancer cell line.","authors":"Elif Zeynep Ozturk, Ebubekir Bakan, Nurcan Kilic Baygutalp, Zafer Bayraktutan","doi":"10.1186/s12860-026-00568-w","DOIUrl":"https://doi.org/10.1186/s12860-026-00568-w","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-18DOI: 10.1186/s12860-026-00565-z
Hadeel A Al-Rawaf, Sami A Gabr, Amir Iqbal, Ahmad H Alghadir
{"title":"Dysregulation of caspase-8 and caspase-9 in T-lymphocyte apoptosis: implications for pathogenesis, diagnosis, and therapeutic targeting in psoriatic arthritis.","authors":"Hadeel A Al-Rawaf, Sami A Gabr, Amir Iqbal, Ahmad H Alghadir","doi":"10.1186/s12860-026-00565-z","DOIUrl":"https://doi.org/10.1186/s12860-026-00565-z","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intracellular Ca<sup>2+</sup> is not essential for SHH signaling but is promoted by Shh ligand in embryonic fibroblasts.","authors":"Xuanming Shi, Zhaomin Wang, Shupeng Li, Yiming Pan, Bing Shen, Shuzhen Liu","doi":"10.1186/s12860-026-00567-x","DOIUrl":"https://doi.org/10.1186/s12860-026-00567-x","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1186/s12860-025-00560-w
Malin A Kjosavik, Katherine L P Downham, Ruth Styfhals, Leonie Adelmann, Marios Chatzigeorgiou, Florian Raible, Pawel Burkhardt, Fergal O'Farrell, Patrick R H Steinmetz, Kathrin Garschall
{"title":"The nascent RNA labelling compound 5-ethynyl uridine (EU) integrates into DNA in some animals.","authors":"Malin A Kjosavik, Katherine L P Downham, Ruth Styfhals, Leonie Adelmann, Marios Chatzigeorgiou, Florian Raible, Pawel Burkhardt, Fergal O'Farrell, Patrick R H Steinmetz, Kathrin Garschall","doi":"10.1186/s12860-025-00560-w","DOIUrl":"10.1186/s12860-025-00560-w","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"4"},"PeriodicalIF":2.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-25DOI: 10.1186/s12860-025-00562-8
Nicholas M Kiger, Nicholas W Mason, Md Ikram Rafid, Jeffrey A Hadwiger
{"title":"Related Dictyostelium G protein subunits Gα1 and Gα2 have different roles in chemotaxis and transcription factor regulation.","authors":"Nicholas M Kiger, Nicholas W Mason, Md Ikram Rafid, Jeffrey A Hadwiger","doi":"10.1186/s12860-025-00562-8","DOIUrl":"10.1186/s12860-025-00562-8","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The differentiation of mesodermal cells (MCs) in the early stage of embryonic development contributes to the organogenesis of several core organs. However, the single-cell molecular architecture of MCs and the key molecular events during the differentiation remain unclear.
Methods: We performed single-cell RNA sequencing (RNA sequencing) and single-cell assay for transposase-accessible chromatin (ATAC-Seq) to analyze the developmental features of MCs to heart, kidney, spleen, liver, and brain in human embryos at gestational ages 7-17 weeks.
Results: We found that EGR1 might be relevant to the differentiation of heterogeneous MC sub-clusters. Meanwhile, RPL10P9+PTMAP5+ MCs had the closest expression profiling with endocardial cells. NDUFA4L2+A2M+ MCs presented the potentials to form endothelial cells (ECs) and hematopoietic stem cells, and MEF2C might be involved in this process.
Conclusions: These findings provide insights into the molecular architecture and lineage progression of MCs during early human embryonic organogenesis, offering a valuable reference for regenerative medicine and organ bioengineering.
{"title":"Molecular architecture of mesoderm cells across early to middle stage of human embryo development at single-cell resolution.","authors":"Wei Zhang, Haiyan Yu, Zhibin Zhang, Dandan Li, Yane Yang, Wei Shi, Wenting Li, Yan Jiang, Wenlong Hu, Zhipeng Zeng, Xinqiong Liu, Zhanye Zheng, Minglin Ou, Donge Tang, Yong Dai","doi":"10.1186/s12860-025-00561-9","DOIUrl":"10.1186/s12860-025-00561-9","url":null,"abstract":"<p><strong>Background: </strong>The differentiation of mesodermal cells (MCs) in the early stage of embryonic development contributes to the organogenesis of several core organs. However, the single-cell molecular architecture of MCs and the key molecular events during the differentiation remain unclear.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (RNA sequencing) and single-cell assay for transposase-accessible chromatin (ATAC-Seq) to analyze the developmental features of MCs to heart, kidney, spleen, liver, and brain in human embryos at gestational ages 7-17 weeks.</p><p><strong>Results: </strong>We found that EGR1 might be relevant to the differentiation of heterogeneous MC sub-clusters. Meanwhile, RPL10P9<sup>+</sup>PTMAP5<sup>+</sup> MCs had the closest expression profiling with endocardial cells. NDUFA4L2<sup>+</sup>A2M<sup>+</sup> MCs presented the potentials to form endothelial cells (ECs) and hematopoietic stem cells, and MEF2C might be involved in this process.</p><p><strong>Conclusions: </strong>These findings provide insights into the molecular architecture and lineage progression of MCs during early human embryonic organogenesis, offering a valuable reference for regenerative medicine and organ bioengineering.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"3"},"PeriodicalIF":2.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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