Cell Discovery最新文献

Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure.

IF 13 1区生物学

Cell Discovery Pub Date : 2025-02-12 DOI: 10.1038/s41421-025-00769-1

Yuqing Zhang, Shourui Hu, Shan Han, Congcong Liu, Xiaofan Liang, Yuxuan Li, Zongxuan Lin, Yiming Qin, Chunxuan Geng, Yue Liu, Linlin Cui, Jingmei Hu, Changming Zhang, Zhao Wang, Xin Liu, Jinlong Ma, Zi-Jiang Chen, Han Zhao

{"title":"Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure.","authors":"Yuqing Zhang, Shourui Hu, Shan Han, Congcong Liu, Xiaofan Liang, Yuxuan Li, Zongxuan Lin, Yiming Qin, Chunxuan Geng, Yue Liu, Linlin Cui, Jingmei Hu, Changming Zhang, Zhao Wang, Xin Liu, Jinlong Ma, Zi-Jiang Chen, Han Zhao","doi":"10.1038/s41421-025-00769-1","DOIUrl":"10.1038/s41421-025-00769-1","url":null,"abstract":"Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet. Mechanistically, compromised insulin secretion underlies this transgenerational susceptibility to diabetes. Integrated analyses of methylome and transcriptome revealed differential DNA methylation of β-cell functional genes in AE-F1 sperm, which was transmitted to AE-F2 islets and further retained in AE-F2 sperm, leading to reduced expression of genes related to insulin secretion, including Pdx1, Irs1, Ptprn2, and Cacna1c. The methylation signatures in AE-F1 sperm were corroborated in diabetic humans and the blood of sons with maternal hyperandrogenism. Moreover, caloric restriction and metformin treatments normalized hyperglycemia in AE-F1 males and blocked their inheritance to offspring by restoring the aberrant sperm DNA methylations. Our findings highlight the transgenerational inheritance of impaired glucose homeostasis in male offspring from maternal AE via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations' metabolic health.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"14"},"PeriodicalIF":13.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human DDIT4L intron retention contributes to cognitive impairment and amyloid plaque formation.

IF 13 1区生物学

Cell Discovery Pub Date : 2025-02-11 DOI: 10.1038/s41421-024-00759-9

Kai-Cheng Li, Hai-Xiang Shi, Zhen Li, Pu You, Jing Pan, Yi-Chuan Cai, Jin-Wen Li, Xue-Fei Ma, Shuo Zhang, Lei Diao, Bing Cai, Hai-Bo Wang, Liang Chen, Ying Mao, Xu Zhang

引用次数: 0

NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters.

IF 13 1区生物学

Cell Discovery Pub Date : 2025-02-11 DOI: 10.1038/s41421-024-00767-9

Héctor I Navarro, Allison E Daly, Benancio Rodriguez, Sunny Wu, Kim A Ngo, Anna Fraser, Allison Schiffman, Yi Liu, Stephen T Smale, Jennifer J Chia, Alexander Hoffmann

{"title":"NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters.","authors":"Héctor I Navarro, Allison E Daly, Benancio Rodriguez, Sunny Wu, Kim A Ngo, Anna Fraser, Allison Schiffman, Yi Liu, Stephen T Smale, Jennifer J Chia, Alexander Hoffmann","doi":"10.1038/s41421-024-00767-9","DOIUrl":"10.1038/s41421-024-00767-9","url":null,"abstract":"A group of autoinflammatory disorders termed relopathies arise as a consequence of NF-κB dysregulation. Genetic loss of the NF-κB subunit RelB in humans and mice leads to autoimmunity and lethal multi-organ inflammatory pathology. Our recent study showed that this inflammatory pathology is independent of type I interferon signaling, and further identified dysregulation of a set of pro-inflammatory NF-κB target genes. However, it remains unknown how the loss of RelB leads to the dysregulation of these NF-κB motif-containing pro-inflammatory genes. Here, we report epigenome profiling studies revealing that RelB is associated with pro-inflammatory genes in dendritic cells. While these genes recruit RelA binding upon exposure to a maturation stimulus, we observed substantially more RelA recruitment in the absence of RelB. For these genes, we found that elevated RelA recruitment is correlated with elevated gene expression. To test whether RelB may compete with RelA for binding to NF-κB-regulated gene promoters via competition for κB sites, we generated a new mouse strain (RelBDB/DB) that harbors targeted point mutations in the RelB DNA binding domain that eliminates high-affinity DNA binding. We found that this targeted mutation in the RelB DNA binding domain is sufficient to drive multi-organ inflammatory pathology. These results provide insights into the biological mechanism of RelB as a suppressor of pro-inflammatory gene expression and autoimmune pathology.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"13"},"PeriodicalIF":13.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A tumor-secreted protein utilizes glucagon release to cause host wasting.

IF 13 1区生物学

Cell Discovery Pub Date : 2025-02-10 DOI: 10.1038/s41421-024-00762-0

Guangming Ding, Yingge Li, Chen Cheng, Kai Tan, Yifei Deng, Huiwen Pang, Zhongyuan Wang, Peixuan Dang, Xing Wu, Elisabeth Rushworth, Yufeng Yuan, Zhiyong Yang, Wei Song

{"title":"A tumor-secreted protein utilizes glucagon release to cause host wasting.","authors":"Guangming Ding, Yingge Li, Chen Cheng, Kai Tan, Yifei Deng, Huiwen Pang, Zhongyuan Wang, Peixuan Dang, Xing Wu, Elisabeth Rushworth, Yufeng Yuan, Zhiyong Yang, Wei Song","doi":"10.1038/s41421-024-00762-0","DOIUrl":"10.1038/s41421-024-00762-0","url":null,"abstract":"Tumor‒host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, is largely unknown. Using the conserved yki3SA-tumor model in Drosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to show that yki3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"11"},"PeriodicalIF":13.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mettl3-m⁶A-NPY axis governing neuron-microglia interaction regulates sleep amount of mice. Mettl3-m6A-NPY轴调节神经元与小胶质细胞之间的相互作用，从而调节小鼠的睡眠量。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-02-04 DOI: 10.1038/s41421-024-00756-y

Qihang Sun, Jinpiao Zhu, Xingsen Zhao, Xiaoli Huang, Wenzheng Qu, Xia Tang, Daqing Ma, Qiang Shu, Xuekun Li

{"title":"Mettl3-m6A-NPY axis governing neuron-microglia interaction regulates sleep amount of mice.","authors":"Qihang Sun, Jinpiao Zhu, Xingsen Zhao, Xiaoli Huang, Wenzheng Qu, Xia Tang, Daqing Ma, Qiang Shu, Xuekun Li","doi":"10.1038/s41421-024-00756-y","DOIUrl":"10.1038/s41421-024-00756-y","url":null,"abstract":"Sleep behavior is regulated by diverse mechanisms including genetics, neuromodulation and environmental signals. However, it remains completely unknown regarding the roles of epitranscriptomics in regulating sleep behavior. In the present study, we showed that the deficiency of RNA m6A methyltransferase Mettl3 in excitatory neurons specifically induces microglia activation, neuroinflammation and neuronal loss in thalamus of mice. Mettl3 deficiency remarkably disrupts sleep rhythm and reduces the amount of non-rapid eye movement sleep. We also showed that Mettl3 regulates neuropeptide Y (NPY) via m6A modification and Mettl3 conditional knockout (cKO) mice displayed significantly decreased expression of NPY in thalamus. In addition, the dynamic distribution pattern of NPY is observed during wake-sleep cycle in cKO mice. Ectopic expression of Mettl3 and NPY significantly inhibits microglia activation and neuronal loss in thalamus, and restores the disrupted sleep behavior of cKO mice. Collectively, our study has revealed the critical function of Mettl3-m6A-NPY axis in regulating sleep behavior.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"10"},"PeriodicalIF":13.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.

IF 13 1区生物学

Cell Discovery Pub Date : 2025-01-28 DOI: 10.1038/s41421-024-00747-z

Yifei Cheng, Xiaofang Chen, Li Feng, Zhicheng Yang, Liyun Xiao, Bin Xiang, Xiaodong Wang, Dongbin Liu, Penghui Lin, Jieyi Shi, Guohe Song, Wulei Qian, Boan Zhang, Yanan Xu, Zheng Gao, Lv Chen, Yingcheng Wu, Jiaqiang Ma, Youpei Lin, Haichao Zhao, Lihua Peng, Xuebin Mao, Yang Liu, Hao Hou, Mingyu Yang, Yuan Ji, Xiaoying Wang, Jian Zhou, Xun Xu, Xiyang Liu, Wu Wei, Xiaoming Zhang, Qiang Gao, Hu Zhou, Yidi Sun, Kui Wu, Jia Fan

{"title":"Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.","authors":"Yifei Cheng, Xiaofang Chen, Li Feng, Zhicheng Yang, Liyun Xiao, Bin Xiang, Xiaodong Wang, Dongbin Liu, Penghui Lin, Jieyi Shi, Guohe Song, Wulei Qian, Boan Zhang, Yanan Xu, Zheng Gao, Lv Chen, Yingcheng Wu, Jiaqiang Ma, Youpei Lin, Haichao Zhao, Lihua Peng, Xuebin Mao, Yang Liu, Hao Hou, Mingyu Yang, Yuan Ji, Xiaoying Wang, Jian Zhou, Xun Xu, Xiyang Liu, Wu Wei, Xiaoming Zhang, Qiang Gao, Hu Zhou, Yidi Sun, Kui Wu, Jia Fan","doi":"10.1038/s41421-024-00747-z","DOIUrl":"10.1038/s41421-024-00747-z","url":null,"abstract":"Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis. We discovered two functional units, one is the intratumor inflammatory hub featured by CAF-FAP plus CD8_PDCD1 proximity and the other is the marginal wound-healing hub with CAF-C7 plus Macrophage_SPP1 co-localization. Inhibiting CAF-FAP combined with anti-PD-1 in orthotopic HCC models led to improved tumor regression than either monotherapy. Collectively, our findings suggest stroma-targeted strategies for HCC based on defined stromal archetypes, raising the concept that CAFs change their transcriptional program and intercellular crosstalk according to the spatial context.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"1"},"PeriodicalIF":13.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells.

IF 13 1区生物学

Cell Discovery Pub Date : 2025-01-28 DOI: 10.1038/s41421-024-00760-2

Guixian Liang, Shicheng Liu, Chunyu Zhou, Mengyao Liu, Yifan Zhang, Dongyuan Ma, Lu Wang, Jing-Dong J Han, Feng Liu

{"title":"Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells.","authors":"Guixian Liang, Shicheng Liu, Chunyu Zhou, Mengyao Liu, Yifan Zhang, Dongyuan Ma, Lu Wang, Jing-Dong J Han, Feng Liu","doi":"10.1038/s41421-024-00760-2","DOIUrl":"10.1038/s41421-024-00760-2","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo. In this work, by engineering vascular niche endothelial cells (VN-ECs), we generated functional HSPCs in vitro from ECs at various sites, including the aorta-gonad-mesonephros (AGM) region and the placenta. Firstly, we converted mouse embryonic HE cells from the AGM region (aHE) into induced HSPCs (iHSPCs), which have the abilities for multilineage differentiation and self-renewal. Mechanistically, we found that VN-ECs can promote the generation of iHSPCs via secretion of CX3CL1 and IL1A. Next, through VN-EC co-culture, we showed that placental HE (pHE) cells, a type of extra-embryonic HE cells, were successfully converted into iHSPCs (pHE-iHSPCs), which have multilineage differentiation capacity, but exhibit limited self-renewal ability. Furthermore, comparative transcriptome analysis of aHE-iHSPCs and pHE-iHSPCs showed that aHE-iHSPCs highly expressed HSC-specific and self-renewal-related genes. Moreover, experimental validation showed that retinoic acid (RA) treatment promoted the transformation of pHE cells into iHSPCs that have self-renewal ability. Collectively, our results suggested that pHE cells possess the potential to transform into self-renewing iHSPCs through RA treatment, which will facilitate the clinical application of placental endothelial cells in hematopoietic cell generation.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"9"},"PeriodicalIF":13.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Apaf-1 is an evolutionarily conserved DNA sensor that switches the cell fate between apoptosis and inflammation. Apaf-1是一种进化上保守的DNA传感器，可以在细胞凋亡和炎症之间切换细胞命运。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-01-21 DOI: 10.1038/s41421-024-00750-4

Jie Ruan, Xuxia Wei, Suizhi Li, Zijian Ye, Linyi Hu, Ru Zhuang, Yange Cao, Shaozhou Wang, Shengpeng Wu, Dezhi Peng, Shangwu Chen, Shaochun Yuan, Anlong Xu

{"title":"Apaf-1 is an evolutionarily conserved DNA sensor that switches the cell fate between apoptosis and inflammation.","authors":"Jie Ruan, Xuxia Wei, Suizhi Li, Zijian Ye, Linyi Hu, Ru Zhuang, Yange Cao, Shaozhou Wang, Shengpeng Wu, Dezhi Peng, Shangwu Chen, Shaochun Yuan, Anlong Xu","doi":"10.1038/s41421-024-00750-4","DOIUrl":"10.1038/s41421-024-00750-4","url":null,"abstract":"Apoptotic protease activating factor 1 (Apaf-1) was traditionally defined as a scaffold protein in mammalian cells for assembling a caspase activation platform known as the 'apoptosome' after its binding to cytochrome c. Although Apaf-1 structurally resembles animal NOD-like receptor (NLR) and plant resistance (R) proteins, whether it is directly involved in innate immunity is still largely unknown. Here, we found that Apaf-1-like molecules from lancelets, fruit flies, mice, and humans have conserved DNA sensing functionality. Mechanistically, mammalian Apaf-1 recruits receptor-interacting protein 2 (RIP2, also known as RIPK2) via its WD40 repeat domain and promotes RIP2 oligomerization to initiate NF-κB-driven inflammation upon cytoplasmic DNA recognition. Furthermore, DNA binding of Apaf-1 determines cell fate by switching the cellular processes between intrinsic stimuli-activated apoptosis and inflammation. These findings suggest that Apaf-1 is an evolutionarily conserved DNA sensor and may serve as a cell fate checkpoint, which determines whether cells initiate inflammation or undergo apoptosis by distinct ligand binding.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"4"},"PeriodicalIF":13.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics. 基于微滴的单细胞高通量三维基因组结构定位与同步转录组学。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-01-21 DOI: 10.1038/s41421-025-00770-8

Honggui Wu, Maoxu Wang, Yinghui Zheng, X Sunney Xie

{"title":"Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics.","authors":"Honggui Wu, Maoxu Wang, Yinghui Zheng, X Sunney Xie","doi":"10.1038/s41421-025-00770-8","DOIUrl":"10.1038/s41421-025-00770-8","url":null,"abstract":"Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its transcriptome co-assay (dscHi-C-multiome) using droplet microfluidics. Using dscHi-C, we investigate chromatin structural changes during mouse brain aging by profiling 32,777 single cells across three developmental stages (3 months, 12 months, and 23 months), yielding a median of 78,220 unique contacts. Our results show that genes with significant structural changes are enriched in pathways related to metabolic process and morphology change in neurons, and innate immune response in glial cells, highlighting the role of 3D genome organization in physiological brain aging. Furthermore, our multi-omics joint assay, dscHi-C-multiome, enables precise cell type identification in the adult mouse brain and uncovers the intricate relationship between genome architecture and gene expression. Collectively, we developed the sensitive, high-throughput dscHi-C and its multi-omics derivative, dscHi-C-multiome, demonstrating their potential for large-scale cell atlas studies in development and disease.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"8"},"PeriodicalIF":13.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of live mice from haploid ESCs with germline-DMR deletions or switch. 生殖系dmr缺失或开关的单倍体ESCs代活小鼠。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-01-21 DOI: 10.1038/s41421-024-00757-x

Yongjian Ma, Meng Yan, Zhenfei Xie, Hongling Zhang, Zhoujie Li, Yuanyuan Li, Suming Yang, Meiling Zhang, Wen Li, Jinsong Li

{"title":"Generation of live mice from haploid ESCs with germline-DMR deletions or switch.","authors":"Yongjian Ma, Meng Yan, Zhenfei Xie, Hongling Zhang, Zhoujie Li, Yuanyuan Li, Suming Yang, Meiling Zhang, Wen Li, Jinsong Li","doi":"10.1038/s41421-024-00757-x","DOIUrl":"10.1038/s41421-024-00757-x","url":null,"abstract":"Genomic imprinting is required for sexual reproduction and embryonic development of mammals, in which, differentially methylated regions (DMRs) regulate the parent-specific monoallelic expression of imprinted genes. Numerous studies on imprinted genes have highlighted their critical roles in development. However, what imprinting network is essential for development is still unclear. Here, we establish a stepwise system to reconstruct a development-related imprinting network, in which diploid embryonic stem cells (ESCs) are derived by fusing between parthenogenetic (PG)- and androgenetic (AG)-haploid embryonic stem cells (haESCs) with different DMR deletions (termed Ha-Ha-fusion system), followed by tetraploid complementation to produce all-haESC fetuses. Diploid ESCs fused between PG-haESCs carrying 8 maternally-derived DMR deletions and AG-haESCs with 2 paternally-derived DMR deletions give rise to live pups efficiently, among which, one lives to weaning. Strikingly, diploid ESCs derived from the fusion of PG-haESCs with 7 maternal DMR deletions and AG-haESCs with 2 paternal DMR deletions and maternal Snrpn-DMR deletion also support full-term embryonic development. Moreover, embryos reconstructed by injection of AG-haESCs with hypomethylated H19-DMR into oocytes with H19-DMR deletion develop into live mice sustaining inverted allelic gene expression. Together, our findings indicate that restoration of monoallelic expression of 10 imprinted regions is adequate for the full-term development of all-haESC pups, and it works irrespective of their parental origins. Meanwhile, Ha-Ha-fusion system provides a useful tool for deciphering imprinting regulation networks during embryonic development.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"5"},"PeriodicalIF":13.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0