Genes & development最新文献_第10页

LINE-1, the NORth star of nucleolar organization 线-1，核仁组织的北极星

IF 10.5 1区生物学

Genes & development Pub Date : 2025-01-10 DOI: 10.1101/gad.352583.124

Misaki Matsuo, Gael Cristofari

引用次数: 0

ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation ESRP2-microRNA-122轴促进出生后肝脏多倍体和成熟的发生

IF 10.5 1区生物学

Genes & development Pub Date : 2025-01-10 DOI: 10.1101/gad.352129.124

Sushant Bangru, Jackie Chen, Nicholas Baker, Diptatanu Das, Ullas V. Chembazhi, Jessica M. Derham, Sandip Chorghade, Waqar Arif, Frances Alencastro, Andrew W. Duncan, Russ P. Carstens, Auinash Kalsotra

{"title":"ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation","authors":"Sushant Bangru, Jackie Chen, Nicholas Baker, Diptatanu Das, Ullas V. Chembazhi, Jessica M. Derham, Sandip Chorghade, Waqar Arif, Frances Alencastro, Andrew W. Duncan, Russ P. Carstens, Auinash Kalsotra","doi":"10.1101/gad.352129.124","DOIUrl":"https://doi.org/10.1101/gad.352129.124","url":null,"abstract":"Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of epithelial splicing regulatory protein 2 (ESRP2) stimulates processing of liver-specific microRNA (miR-122) to facilitate polyploidization, maturation, and functional competence of hepatocytes. By determining transcriptome-wide protein–RNA interactions in vivo and integrating them with single-cell and bulk hepatocyte RNA-seq data sets, we delineated an ESRP2-driven RNA processing program that drives sequential replacement of fetal-to-adult transcript isoforms. Specifically, ESRP2 binds the primary miR-122 host gene transcript to promote its processing/biogenesis. Combining constitutive and inducible ESRP2 gain- and loss-of-function mouse models with miR-122 rescue experiments, we demonstrated that timed activation of ESRP2 augments the miR-122-driven program of cytokinesis failure, ensuring the proper onset and extent of hepatocyte polyploidization.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"319 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges. 通过空间转录组学解读正常和癌症干细胞龛位：机遇与挑战。

IF 7.5 1区生物学

Genes & development Pub Date : 2025-01-07 DOI: 10.1101/gad.351956.124

Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang

{"title":"Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges.","authors":"Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang","doi":"10.1101/gad.351956.124","DOIUrl":"10.1101/gad.351956.124","url":null,"abstract":"Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional plasticity. Investigating these properties across diverse organs during normal development and tumorigenesis is of paramount research interest and translational potential. Advancements in next-generation sequencing (NGS), single-cell transcriptomics, and spatial transcriptomics have ushered in a new era in cancer research, providing high-resolution and comprehensive molecular maps of diseased tissues. Various spatial technologies, with their unique ability to measure the location and molecular profile of a cell within tissue, have enabled studies on intratumoral architecture and cellular cross-talk within the specific niches. Moreover, delineation of spatial patterns for niche-specific properties such as hypoxia, glucose deprivation, and other microenvironmental remodeling are revealed through multilevel spatial sequencing. This tremendous progress in technology has also been paired with the advent of computational tools to mitigate technology-specific bottlenecks. Here we discuss how different spatial technologies are used to identify NSCs and CSCs, as well as their associated niches. Additionally, by exploring related public data sets, we review the current challenges in characterizing such niches, which are often hindered by technological limitations, and the computational solutions used to address them.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"64-85"},"PeriodicalIF":7.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575831","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

Genes & Development aims for an expansive horizon 基因与发展的目标是一个广阔的视野

IF 10.5 1区生物学

Genes & development Pub Date : 2025-01-01 DOI: 10.1101/gad.352534.124

Andrew Dillin

引用次数: 0

Genes & Development: an evolution 基因与发育：一种进化

IF 10.5 1区生物学

Genes & development Pub Date : 2025-01-01 DOI: 10.1101/gad.352552.124

John R. Inglis

引用次数: 0

E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells E3连接酶底物适配器SPOP微调胰腺β细胞的UPR

IF 10.5 1区生物学

Genes & development Pub Date : 2024-12-30 DOI: 10.1101/gad.352010.124

Alexis U. Oguh, Matthew W. Haemmerle, Sabyasachi Sen, Andrea V. Rozo, Shristi Shrestha, Jean-Philippe Cartailler, Hossein Fazelinia, Hua Ding, Sam Preza, Juxiang Yang, Xiaodun Yang, Lori Sussel, Juan R. Alvarez-Dominguez, Nicolai Doliba, Lynn A. Spruce, Rafael Arrojo e Drigo, Doris A. Stoffers

{"title":"E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells","authors":"Alexis U. Oguh, Matthew W. Haemmerle, Sabyasachi Sen, Andrea V. Rozo, Shristi Shrestha, Jean-Philippe Cartailler, Hossein Fazelinia, Hua Ding, Sam Preza, Juxiang Yang, Xiaodun Yang, Lori Sussel, Juan R. Alvarez-Dominguez, Nicolai Doliba, Lynn A. Spruce, Rafael Arrojo e Drigo, Doris A. Stoffers","doi":"10.1101/gad.352010.124","DOIUrl":"https://doi.org/10.1101/gad.352010.124","url":null,"abstract":"The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific Spop deletion mouse strain (SpopβKO) and found that Spop is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux. Integration of proteomic, TF-regulatory gene network, and biochemical analyses identified XBP1 as a functionally important SPOP substrate in pancreatic β cells. Furthermore, loss of SPOP strengthened the IRE1α–XBP1 axis of unfolded protein response (UPR) signaling. ER stress promoted proteasomal degradation of SPOP, supporting a model whereby SPOP fine-tunes XBP1 activation during the UPR. These results position SPOP as a regulator of β-cell function and proper UPR activation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"36 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternative splicing controls pan-neuronal homeobox gene expression 选择性剪接控制泛神经元同源盒基因表达

IF 10.5 1区生物学

Genes & development Pub Date : 2024-12-27 DOI: 10.1101/gad.352184.124

Eduardo Leyva-Díaz, Michael Cesar, Karinna Pe, José Ignacio Jordá-Llorens, Jessica Valdivia, Oliver Hobert

{"title":"Alternative splicing controls pan-neuronal homeobox gene expression","authors":"Eduardo Leyva-Díaz, Michael Cesar, Karinna Pe, José Ignacio Jordá-Llorens, Jessica Valdivia, Oliver Hobert","doi":"10.1101/gad.352184.124","DOIUrl":"https://doi.org/10.1101/gad.352184.124","url":null,"abstract":"The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of Caenorhabditis elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 (“CASP of nematodes”) in C. elegans. How gene expression from this complex locus is controlled—and, in C. elegans, directed to all cells of the nervous system—has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75, the C. elegans homolog of vertebrate CELF proteins. During embryogenesis, the cone-1&ceh-44 locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript exclusively in the nervous system. Hence, UNC-75/CELF-mediated alternative splicing not only directs pan-neuronal gene expression but also excludes a phylogenetically deeply conserved golgin from the nervous system, paralleling surprising spatial specificities of another golgin that we describe here as well. Our findings provide novel insights into how all cells in a nervous system acquire pan-neuronal identity features and reveal unanticipated cellular specificities in Golgi apparatus composition.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"15 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NKX2.2 and KLF4 cooperate to regulate α-cell identity NKX2.2和KLF4协同调节α-细胞身份

IF 10.5 1区生物学

Genes & development Pub Date : 2024-12-20 DOI: 10.1101/gad.352193.124

Elliott P. Brooks, McKenna R. Casey, Kristen L. Wells, Tsung-Yun Liu, Madeline Van Orman, Lori Sussel

{"title":"NKX2.2 and KLF4 cooperate to regulate α-cell identity","authors":"Elliott P. Brooks, McKenna R. Casey, Kristen L. Wells, Tsung-Yun Liu, Madeline Van Orman, Lori Sussel","doi":"10.1101/gad.352193.124","DOIUrl":"https://doi.org/10.1101/gad.352193.124","url":null,"abstract":"Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.2 is critical for the identity of pancreatic islet α cells by directly activating α-cell genes and repressing alternate islet cell fate genes. When compared with the known role of NKX2.2 in islet β cells, we demonstrate that NKX2.2 regulates α-cell genes, facilitated in part by α-cell-specific DNA binding at gene promoters. Furthermore, we have identified the reprogramming factor KLF4 as having enriched expression in α cells, where it co-occupies NKX2.2-bound α-cell promoters, is necessary for NKX2.2 promoter occupancy in α cells, and coregulates many NKX2.2 α-cell transcriptional targets. Overexpression of Klf4 in β cells is sufficient to manipulate chromatin accessibility, increase binding of NKX2.2 at α-cell-specific promoter sites, and alter expression of NKX2.2-regulated cell-specific targets. This study identifies KLF4 as a novel α-cell factor that cooperates with NKX2.2 to regulate α-cell identity.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"93 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells 卵细胞对动物卵巢生殖细胞piRNA通路的转录调控

IF 10.5 1区生物学

Genes & development Pub Date : 2024-12-20 DOI: 10.1101/gad.352120.124

Azad Alizada, Gregory J. Hannon, Benjamin Czech Nicholson

{"title":"Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells","authors":"Azad Alizada, Gregory J. Hannon, Benjamin Czech Nicholson","doi":"10.1101/gad.352120.124","DOIUrl":"https://doi.org/10.1101/gad.352120.124","url":null,"abstract":"The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using Drosophila as a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells. Ectopic expression of Ovo in ovarian somatic cells activates germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3, and Vasa, leading to assembly of perinuclear cellular structures resembling nuage bodies of germ cells. We found that in ovarian somatic cells, transcription of ovo is repressed by l(3)mbt, thus preventing expression of germline piRNA pathway genes in the soma. Cross-species ChIP-seq and motif analyses demonstrate that Ovo is binding to genomic CCGTTA motifs within the promoters of germline piRNA pathway genes, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. Our results also show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from insects to humans.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"147 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells rDNA重复序列远端连接处的LINE1元件调节人胚胎干细胞的核仁组织

IF 10.5 1区生物学

Genes & development Pub Date : 2024-12-20 DOI: 10.1101/gad.351979.124

Lamisa Ataei, Juan Zhang, Simon Monis, Krystyna Giemza, Kirti Mittal, Joshua Yang, Mayu Shimomura, Brian McStay, Michael D. Wilson, Miguel Ramalho-Santos

{"title":"LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells","authors":"Lamisa Ataei, Juan Zhang, Simon Monis, Krystyna Giemza, Kirti Mittal, Joshua Yang, Mayu Shimomura, Brian McStay, Michael D. Wilson, Miguel Ramalho-Santos","doi":"10.1101/gad.351979.124","DOIUrl":"https://doi.org/10.1101/gad.351979.124","url":null,"abstract":"The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes. Distal junctions (DJs) are ∼400 kb sequences adjacent to rDNA arrays that are thought to anchor them at the nucleolus, although the underlying regulatory elements remain unclear. Here we show that DJs display a dynamic chromosome conformation profile in human embryonic stem cells (hESCs). We identified a primate-specific, full-length insertion of the retrotransposon long interspersed nuclear element 1 (LINE1) in a conserved position across all human DJs. This DJ-LINE1 locus interacts with specific regions of the DJ and is upregulated in naïve hESCs. CRISPR-based deletion and interference approaches revealed that DJ-LINE1 contributes to nucleolar positioning of the DJs. Moreover, we found that the expression of DJ-LINE1 is required for maintenance of the structure and transcriptional output of the nucleolus in hESCs. Silencing of DJ-LINE1 leads to loss of self-renewal, disruption of the landscape of chromatin accessibility, and derepression of earlier developmental programs in naïve hESCs. This work uncovers specific LINE1 elements with a fundamental role in nucleolar organization in hESCs and provides new insights into how the nucleolus functions as a key genome-organizing hub.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"13 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0