Article
Multidisciplinary Sciences
Elisa Pedone, Mario Failli, Gennaro Gambardella, Rossella De Cegli, Antonella La Regina, Diego di Bernardo, Lucia Marucci
Summary: This study found that moderate beta-catenin levels play an important role in cell differentiation, promoting the formation of EpiLC in vitro.
Article
Biochemistry & Molecular Biology
Fabiana Passaro, Ilaria De Martino, Federico Zambelli, Giorgia Di Benedetto, Matteo Barbato, Anna Maria D'Erchia, Caterina Manzari, Graziano Pesole, Margherita Mutarelli, Davide Cacchiarelli, Dario Antonini, Silvia Parisi, Tommaso Russo
Summary: This study reveals a new role for YAP in governing the epigenetic dynamics of pluripotency exit. Transient downregulation of YAP leads to genome-wide alteration of DNA methylation remodeling during ESC differentiation, potentially involving the regulation of molecules such as RNA ephemeron and Dnmt3l.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Lucy LeBlanc, Mijeong Kim, Aparna Kambhampati, Albert J. Son, Nereida Ramirez, Jonghwan Kim
Summary: Cell density impacts gene expression and differentiation in mouse embryonic stem cells; β-catenin is primarily at adherens junctions at high density but translocates to the nucleus at low density; Esrrb maintains pluripotency gene expression at high density and decreases DNA association at low density.
Article
Multidisciplinary Sciences
Andrea Lauria, Guohua Meng, Valentina Proserpio, Stefania Rapelli, Mara Maldotti, Isabelle Laurence Polignano, Francesca Anselmi, Danny Incarnato, Anna Krepelova, Daniela Donna, Chiara Levra Levron, Giacomo Donati, Ivan Molineris, Francesco Neri, Salvatore Oliviero
Summary: The establishment of DNA methylation patterns during mouse early development is crucial for cell fate determination. However, the specific molecular targets and mechanisms of de novo methylation machinery during differentiation are not fully understood. In this study, the researchers identified DNMT3B-dependent regulatory elements that play a critical role in cell fate determination. They found that DNMT3B-dependent DNA methylation is essential for proper differentiation and lineage determination, and ectopic expression of DNMT3B can restore normal gene expression and cell fate. This study provides important insights into the role of DNA methylation in early development and cell fate determination.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Xinpeng Wen, Zesong Lin, Hao Wu, Lanrui Cao, Xudong Fu
Summary: In this study, the researchers identified a novel regulator, Zfp281, for the pluripotent-to-totipotent transition in mouse embryonic stem cells. They found that Zfp281 inhibits the transition by repressing transcripts upregulated during the 2C-like transition, and this inhibitory effect leads to impaired 2C-like transition ability in primed-state cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Thulaj Meharwade, Loick Joumier, Maxime Parisotto, Vivian Huynh, Edroaldo Lummertz da Rocha, Mohan Malleshaiah
Summary: Embryonic stem cells can simulate multiple states resembling different stages of early embryogenesis, and bone morphogenetic protein (BMP) signaling can induce the totipotent state. Cross-activated pathways can constrain the role of BMP, but by inhibiting these pathways, we can enhance the proportion of totipotent cells.
Article
Chemistry, Multidisciplinary
Yingjie Hang, Xiaoliang Ma, Chunxiao Liu, Siyuan Li, Sixuan Zhang, Ruyan Feng, Qianwen Shang, Qi Liu, Zhaozhao Ding, Xiaoyi Zhang, Liyin Yu, Qiang Lu, Changshun Shao, Hong Chen, Yufang Shi, Jiuyang He, David L. Kaplan
Summary: The development of anisotropic silk protein nanofiber-based hydrogels enables mouse embryonic stem cells to maintain stemness in vitro without the need for leukemia inhibitory factor and mouse embryonic fibroblasts, resulting in superior pluripotency and genetic stability. The hydrogels establish an improved dynamic niche that stimulates autocrine factor secretion and maintains pluripotency and propagation of ESCs, offering a simple and cost-effective option for expansion and utility of ESCs in research and therapy, while providing insights into early mammalian embryogenesis.
Article
Cell & Tissue Engineering
Martin Bergert, Sergio Lembo, Sumana Sharma, Luigi Russo, Danica Milovanovic, Kristjan H. Gretarsson, Mandy Boermel, Pierre A. Neveu, Jamie A. Hackett, Evangelia Petsalaki, Alba Diz-Munoz
Summary: Cell membrane mechanics play a crucial role in the exit from naive pluripotency of mouse embryonic stem cells, with a decrease in membrane-to-cortex attachment identified as an essential cell-intrinsic mechanism for differentiation.
Article
Cell Biology
Haibin Jiang, Mingxia Du, Yaning Li, Tengfei Zhou, Jia Lei, Hongqing Liang, Zhen Zhong, Rafia S. Al-Lamki, Ming Jiang, Jun Yang
Summary: It has been found that ID1 and ID3 play important roles in the survival and pluripotency of hESCs, regulating the transition between primed and naive-like states through the AKT signaling pathway. TCF3 mediates transcriptional inhibition of MCL1 to promote AKT phosphorylation.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Yumei Jia, Zhaoyuan Guo, Jiahao Zhu, Guanyu Qin, Wenwen Sun, Yu Yin, Haiying Wang, Renpeng Guo
Summary: The study shows that Snap29 plays a crucial role in the self-renewal and differentiation of mouse ESCs. Depletion of Snap29 does not affect the self-renewal and pluripotency-associated factor expression in ESCs, but enhances their differentiation into cardiomyocytes. Transcriptome analysis reveals that Snap29 deficiency significantly decreases the expression of genes required for germ layer differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Fuquan Chen, Xiaomin Li, Xiao Feng, Tingting Gao, Weiyu Zhang, Zhi Cheng, Xuan Zhao, Ruiqing Chen, Xinyi Lu
Summary: In this study, lncRNA Lx8-SINE B2 was identified as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.
Article
Cell & Tissue Engineering
Seong-Min Kim, Eun-Ji Kwon, Yun-Jeong Kim, Young-Hyun Go, Ji-Young Oh, Seokwoo Park, Jeong Tae Do, Keun-Tae Kim, Hyuk-Jin Cha
Summary: This study discovered the differential roles of Shp2 in naive and primed pluripotency and proposed the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naive pluripotency.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Multidisciplinary Sciences
Bercin K. Cenik, Christie C. Sze, Caila A. Ryan, Siddhartha Das, Kaixiang Cao, Delphine Douillet, Emily J. Rendleman, Didi Zha, Nabiha Haleema Khan, Elizabeth Bartom, Ali Shilatifard
Summary: This study reveals that Set1A/COMPASS and ING5 may play crucial roles in regulating the self-renewal and differentiation status of ESCs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Anderson Tan, Renuka Prasad, Eek-hoon Jho
Summary: TFEB plays a crucial role in mESCs by regulating PTN to maintain pluripotency, with interactions involving Nanog and Sox2. While high levels of TFEB are expected to enhance autophagy-lysosomal activity, undifferentiated mESCs surprisingly display low basal levels.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Sue Yu, Jia Li, Guanxu Ji, Zhen Long Ng, Jiamin Siew, Wan Ning Lo, Ying Ye, Yuan Yuan Chew, Yun Chau Long, Wensheng Zhang, Ernesto Guccione, Yuin Han Loh, Zhi-Hong Jiang, Henry Yang, Qiang Wu
Summary: Chromatin modification is crucial for pluripotency maintenance in embryonic stem cells. Npac, a reader of H3K36me3, is essential for the transcriptional elongation of pluripotency genes by interacting with RNA Pol II and positive transcription elongation factor b.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Sandhya Malla, Devi Prasad Bhattarai, Paula Groza, Dario Melguizo-Sanchis, Ionut Atanasoai, Carlos Martinez-Gamero, Angel-Carlos Roman, Dandan Zhu, Dung-Fang Lee, Claudia Kutter, Francesca Aguilo
Summary: This study reveals the role of ZFP207 in mouse embryonic stem cells through multiple functional analyses. Unlike human ESCs, mouse ZFP207 mainly exerts its effects by controlling AS networks and acting as RNA-binding proteins (RBPs) to maintain ESC identity and regulate neural fate commitment.
Article
Multidisciplinary Sciences
Jian Tu, Zijun Huo, Yao Yu, Dandan Zhu, An Xu, Mo-Fan Huang, Ruifeng Hu, Ruoyu Wang, Julian A. Gingold, Yi-Hung Chen, Kuang-Lei Tsai, Nicolas R. Forcioli-Conti, Sarah X. L. Huang, Thomas R. Webb, Jie Su, Danielle A. Bazer, Peilin Jia, Jason T. Yustein, Lisa L. Wang, Mien-Chie Hung, Zhongming Zhao, Chad D. Huff, Jingnan Shen, Ruiying Zhao, Dung-Fang Lee
Summary: The study reveals that the spliceosome is an up-regulated target in RB1-mutant cells responding to oncogenic stress, and pRB and E2F3a coregulate spliceosomal gene expression, affecting cell proliferation and tumorigenesis. These findings suggest that the spliceosomal machinery could be a potential therapeutic vulnerability for pRB-deficient cancers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Amin R. Mazloom, Huilei Xu, Jaume Reig-Palou, Ana Vasileva, Angel-Carlos Roman, Sonia Mulero-Navarro, Ihor R. Lemischka, Ana Sevilla
Summary: This study describes the transcriptional regulatory circuitry of embryonic stem cells based on miRNA array expression and short transcript sequencing, revealing the regulatory role of Estrogen Related Receptor Beta and its dynamic changes during cell differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Yi-Hung Chen, Pei-San Huang, Meng-Hsuan Wen, Manhua Pan, Dung-Fang Lee, Tai-Yen Chen
Summary: A homozygous knock-in human embryonic stem cell clone expressing photoconvertible fluorescence protein tagged endogenous CTR1 has been successfully generated, allowing the study of CTR1 at an endogenous level in different cellular contexts.
STEM CELL RESEARCH
(2022)
Article
Medicine, General & Internal
Hong -Bo Li, Gang Huang, Jian Tu, Dong-Ming Lv, Qing-Lin Jin, Jun -Kai Chen, Yu -Tong Zou, Dung -Fang Lee, Jing-Nan Shen, Xian-Biao Xie
Summary: The study unveiled the abundance of m(6)A modifications in osteosarcoma (OS) and identified the oncogenic role of METTL14 in OS progression. MN1 was revealed as a downstream gene of METTL14, contributing to tumor progression and chemotherapy resistance. Mechanistically, MN1 is methylated by METTL14 in the coding sequence, recognized by IGF2BP2 to facilitate translation efficiency.
Editorial Material
Cell Biology
Veronica Gonzalez-Fernandez, Ana Sevilla
Article
Oncology
Paolo Petazzi, Laia Miquel-Serra, Sergio Huertas, Cecilia Gonzalez, Neus Boto, Eduardo Muniz-Diaz, Pablo Menendez, Ana Sevilla, Nuria Nogues
Summary: The limited availability of red cells with extremely rare blood group phenotypes has led to the search for alternative sources of pluripotent cells for the generation of these rare blood types. This study presents a CRISPR/Cas9-mediated gene editing strategy to convert blood type A to universal type O, and successfully applies it to an Rh-null donor-derived hiPSC line. This research provides an example for potential application to other hiPSC lines derived from rare blood donors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Editorial Material
Cell & Tissue Engineering
Dung-Fang Lee, Carlos-Filipe Pereira
CELLULAR REPROGRAMMING
(2023)
Editorial Material
Cell & Tissue Engineering
Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee
Summary: By analyzing the transcriptional trajectories and epigenomic traits of reprogramming and transforming cells at the single-cell level, Huyghe et al identified two key transcription factors, Bcl11b and Atoh8, that control cell plasticity during pluripotent reprogramming and oncogenic transformation.
CELLULAR REPROGRAMMING
(2022)
Article
Oncology
Dhruv Chachad, Lalit R. Patel, Carlos Vera Recio, Rasoul Pourebrahim, Elizabeth M. Whitley, Wenyi Wang, Xiaoping Su, An Xu, Dung-Fang Lee, Guillermina Lozano
Summary: Missense mutations in the DNA binding domain of p53 can be structural or contact mutations, affecting the protein's conformation. These mutations have gain-of-function activities and interact with transcription factors to promote increased metastatic potential. Mouse models expressing the p53 mutants specifically in osteoblasts show decreased survival and increased metastasis compared to p53-null mice. RNA sequencing reveals distinct gene expression profiles and interactions with different transcription factors for each mutant, and validation experiments demonstrate the role of p53R245W in driving migration and invasion in osteosarcoma. These findings identify unique mechanisms of action for the p53 mutants.
Article
Hematology
Luena Papa, Tiphaine C. Martin, Mansour Djedaini, Mahtab Zangui, Umut Ozbek, Ramon Parsons, Ronald Hoffman, Christoph Schaniel
Summary: The regenerative potential of human hematopoietic stem cells (HSCs) relies on their ability to provide life-long blood cell production and repopulate myeloablated allogeneic transplant recipients. The expansion of HSC numbers during ex vivo culture is influenced by both HSC divisions and their adaptation to metabolic stress. Reprogramming of human CD34+ hematopoietic stem and progenitor cells (HSPCs), combined with cytokines and an epigenetic modifier, leads to an increased number of phenotypic HSCs with long-term repopulation capacity. This process is accompanied by an upregulation of genes involved in metabolic integrity, including SIRT1 and SIRT3.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Oncology
Joshua H. Choe, Tatsuya Kawase, An Xu, Asja Guzman, Aleksandar Z. Obradovic, Ana Maria Low-Calle, Bita Alaghebandan, Ananya Raghavan, Kaitlin Long, Paul M. Hwang, Joshua D. Schiffman, Yan Zhu, Ruiying Zhao, Dung -Fang Lee, Chen Katz, Carol Prives
Summary: This study investigates the pathogenic mechanism of cancer susceptibility genes and finds that the p53(A347D) mutation leads to the inability of p53 to form tetramers, resulting in a hyperstable dimeric state and the inability to bind and activate most canonical p53 target genes, but possessing neomorphic functions. Cells with the p53(A347D) mutation have similar tumorigenic capabilities compared to cells without p53, but the mutation can induce metabolic reprogramming and severe mitochondrial network abnormalities, and can drive apoptotic cell death via mitochondrial association in the absence of transcriptional activity upon topoisomerase II inhibition.
Article
Cell Biology
Leire Pedrosa, Carmen Bedia, Dioulde Diao, Alejandra Mosteiro, Abel Ferres, Elisabetta Stanzani, Fina Martinez-Soler, Avelina Tortosa, Estela Pineda, Iban Aldecoa, Marc Centellas, Marta Munoz-Tuduri, Ana Sevilla, Angels Sierra, Jose Juan Gonzalez Sanchez
Summary: This study investigated the effects of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) on glioblastoma (GB) treatment and determined the optimal conditions for PDT efficacy without causing phototoxic injury to normal brain tissue. The results showed that 5-ALA/PDT effectively inhibited cancer cell proliferation and promoted apoptosis without significant effects on normal cells.
Article
Biology
Wanqiu Chen, Chenguang Wang, Zhi-Xue Yang, Feng Zhang, Wei Wen, Christoph Schaniel, Xianqiang Mi, Matthew Bock, Xiao-Bing Zhang, Hongyu Qiu, Charles Wang
Summary: Researchers have developed a method to generate induced mesenchymal stromal cells (iMSCs) by directly reprogramming human peripheral blood mononuclear cells (PBMCs) using five factors. Omission of OCT4, one of the factors, significantly impairs the functionality of iMSCs and downregulates MSC-specific and mesoderm-regulating genes. The transient expression of OCT4 increases chromatin accessibility and promotes demethylation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Analytical
Jaskirat Singh Batra, Ting-Yen Chi, Mo-Fan Huang, Dandan Zhu, Zheyuan Chen, Dung-Fang Lee, Jun Kameoka
Summary: This study developed a wearable paper-based virus sensor based on molecular imprinting technique and conductive polyaniline, which can detect and monitor potential virus infections. This sensor can be integrated with a face mask, offering an alternative approach to virus monitoring in communities.
