Review
Oncology
Siwei Deng, Yuliang Feng, Siim Pauklin
Summary: This review discusses the importance of three-dimensional chromatin structures in biological processes and diseases, as well as the key structural protein elements involved in chromatin interactions. The recent development of technologies and bioinformatics approaches for studying chromatin interactions in gene expression regulation is also summarized.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yezhang Zhu, Jiali Yu, Jiahui Gu, Chaoran Xue, Long Zhang, Jiekai Chen, Li Shen
Summary: The 3D genome organization plays a critical role in acquiring totipotency, as demonstrated in a study using mouse embryonic stem cells. The transition from pluripotent to totipotent-like state involves changes in chromatin architecture, enhancer-promoter interactions, and gene regulation, highlighting the importance of chromatin organization in cell fate determination. Disruption of chromatin structure promotes the ESC to 2CLC transition, emphasizing the functional significance of 3D genome organization in totipotency acquisition.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Aiendrila Roy, Swati Shree Padhi, Ibakordor Khyriem, Saket Nikose, S. H. Harsha Sankar, Ruthrotha Selvi Bharathavikru
Summary: This article summarizes recent research on methylation dynamics and how it is reset during differentiation and de-differentiation. Methylation plays a crucial role in stem cell pluripotency and differentiation, and regulates cellular stress pathways in immune responses such as inflammation and cancer stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carolina Villarroya-Beltri, Ana Filipa B. Martins, Alejandro Garcia, Daniel Gimenez, Eduardo Zarzuela, Monica Novo, Cristina Del Alamo, Jose Gonzalez-Martinez, Gloria C. Bonel-Perez, Irene Diaz, Maria Guillamot, Massimo Chiesa, Ana Losada, Osvaldo Grana-Castro, Meritxell Rovira, Javier Munoz, Maria Salazar-Roa, Marcos Malumbres
Summary: Maintenance of stemness is regulated by CDC14, a CDK-counteracting phosphatase, which dephosphorylates UTF1 to trigger its degradation and control neural differentiation. Lack of CDC14 results in deficient neural system development and impaired neural differentiation from ESCs. CDC14 phosphatases are critical molecular switches linking cell cycle regulation and self-renewal.
Review
Chemistry, Medicinal
Sorayya Ghasemi, Suowen Xu, Seyed Mohammad Nabavi, Mohammad Amir Amirkhani, Antoni Sureda, Silvia Tejada, Zahra Lorigooini
Summary: Epigenetic alterations play a significant role in cancer development, especially in cancer stem cells (CSCs). Epigenetic therapies targeting CSCs are emerging as a promising strategy for cancer treatment, with phenolic compounds potentially neutralizing CSCs development and metabolism through epigenetic mechanisms.
PHYTOTHERAPY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Yongping Lin, Feng Zhang, Shaojie Chen, Xiyu Zhu, Jincheng Jiao, Yike Zhang, Zhaomin Li, Jiao Lin, Biao Ma, Minglong Chen, Peng-Yuan Wang, Chang Cui
Summary: Biophysical cues have been found to promote the cardiac differentiation of human pluripotent stem cells (hPSCs), but the underlying mechanism remains unclear. In this study, the use of a binary colloidal crystal substrate called 5PM was shown to influence the cell nucleus, cytoskeleton, and epigenetic states of hPSCs, leading to changes in chromatin accessibility and histone modifications. The effect was found to be dependent on cytoskeleton tension and the nuclear accumulation of SETDB1, a histone lysine methyltransferase. Knockdown of SETDB1 reversed the promotive effects of the 5PM on cardiac differentiation. Similar results were observed in human embryonic stem cells, suggesting that the biophysical impact of the 5PM surfaces on cardiac differentiation may be universal.
Article
Biochemical Research Methods
Spiro C. Stilianoudakis, Maggie A. Marshall, Mikhail G. Dozmorov
Summary: The preciseTAD framework, trained on high-resolution genome annotation data, accurately predicts 3D domain boundaries at base-pair resolution, providing a new tool for better understanding how genomic regulators shape the 3D structure of the genome.
Review
Medicine, General & Internal
Chang Liu, Xing Feng, Guoping Li, Priyanka Gokulnath, Junjie Xiao
Summary: Human pluripotent stem cell (hPSC) technology provides abundant opportunities for disease modeling. Cardiomyocytes derived from hPSCs are efficient tools for studying cardiac diseases, drug screening, and pathological mechanisms. This review discusses the advantages and limitations of the 2D hPSC-cardiomyocyte system and introduces recent developments in 3D culture platforms derived from hPSCs.
Article
Biochemistry & Molecular Biology
Jacqueline Chyr, Zhigang Zhang, Xi Chen, Xiaobo Zhou
Summary: In this study, a machine-learning model called PredTAD was used to explore the relationship between multi-omics data and higher-order chromatin structures, leading to the discovery of the ability to predict boundary changes using simple data and identifying TAD boundary alterations involved in important signaling pathways and oncogene expression in the breast cancer genome.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Yu Zhao, Yingzhe Ding, Liangqiang He, Qin Zhou, Xiaona Chen, Yuying Li, Maria Vittoria Alfonsi, Zhenguo Wu, Hao Sun, Huating Wang
Summary: This study comprehensively maps the reorganization of the three-dimensional genome in skeletal muscle stem cells, revealing its importance in cell activation and aging. It also identifies key factors and elements involved in chromatin organization and gene expression.
Article
Medicine, Research & Experimental
Edit Gara, Eleonora Zucchelli, Annamaria Nemes, Zoltan Jakus, Kitti Ajtay, Eva Kemecsei, Gabor Kiszler, Nikolett Hegedus, Krisztian Szigeti, Ivan Foldes, Kristof Arvai, Janos Kosa, Kraszimir Kolev, Erzsebet Komorowicz, Parasuraman Padmanabhan, Pal Maurovich-Horvat, Edit Dosa, Gyorgy Varady, Miklos Polos, Istvan Hartyanszky, Sian E. Harding, Bela Merkely, Domokos Mathe, Gabor Szabo, Tamas Radovits, Gabor Foldes
Summary: This study demonstrates that the combination of human induced pluripotent stem cell-derived endothelial cells (hPSC-EC) and biomatrices has the potential to repair ischemic tissues by reconstructing vascular structures and functions. In vitro and in vivo experiments showed that these cells can develop beneficial properties such as antifibrotic, vasoactive and anti-inflammatory effects during recellularization.
Article
Oncology
Olga A. Sukocheva, Elena Lukina, Markus Friedemann, Mario Menschikowski, Albert Hagelgans, Gjumrakch Aliev
Summary: This article discusses recent advances in the epigenetic regulation of endocrine drug resistance and evaluates novel anti-resistance strategies. It has been found that epigenetic mechanisms can effectively silence ER expression and facilitate the development of endocrine resistance in breast cancer cells. Targeted inhibition of specific epigenetic tools can recover ER expression and increase sensitivity to anti-estrogens, preventing the selection of resistant cells and cancer stem cell survival.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biology
Diyan Li, Mengnan He, Qianzi Tang, Shilin Tian, Jiaman Zhang, Yan Li, Danyang Wang, Long Jin, Chunyou Ning, Wei Zhu, Silu Hu, Keren Long, Jideng Ma, Jing Liu, Zhihua Zhang, Mingzhou Li
Summary: The three-dimensional architecture of the genome plays a crucial role in gene expression regulation and conservation across species. This study compares the 3D genomes of fish, chickens, and 10 mammalian species, and reveals that genome size and chromosome length influence the higher hierarchical organization of the genome, while local transcriptional availability is selected through vertebrate evolution. Additionally, conservation of topologically associating domains is associated with modularity of expression profiles, and LINE and SINE transposable elements contribute to heterochromatin and euchromatin organization during genome evolution.
Article
Chemistry, Multidisciplinary
Deogil Kim, Byung-Hyun Cha, Jinsung Ahn, Yoshie Arai, Bogyu Choi, Soo-Hong Lee
Summary: Understanding the biophysical relationships between stem cells and applied biomaterials is crucial in controlling stem cell functions. This study highlights the significant role of 3D microenvironment, particularly methacrylated hyaluronic acid (HA) hydrogel, in improving cellular reprogramming into iPSCs. The incorporation of cues from the 3D microenvironment accelerates the reprogramming process, offering potential advantages for translational applications.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Review
Cell Biology
Genie Min Ju Wu, Andy Chun Hang Chen, William Shu Biu Yeung, Yin Lau Lee
Summary: Mammalian female reproduction relies on the functionality of the ovary, which is determined by the quality of ovarian follicles. Recent studies have successfully generated ovarian follicles in-vitro from pluripotent stem cells. These cells hold the potential to form ovarian follicles or organoids when co-cultured with ovarian somatic cells. In addition, oocytes isolated from these organoids have been shown to be capable of fertilization in-vitro. While the efficiency of in-vitro folliculogenesis remains low, the establishment of pluripotent stem cell-based models provides valuable insights into folliculogenesis. This article reviews the developmental events during in-vivo follicular development and discusses the progress of generating primordial germ cell-like cells (PGCLCs), pre-granulosa cells, and theca cells in-vitro.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Letter
Gastroenterology & Hepatology
Yuliang Feng, Mai Abdel Mouti, Siim Pauklin
Review
Oncology
Rhiannon French, Siim Pauklin
Summary: Cancer stem cells (CSCs) possess stem-like properties and play a crucial role in tumor initiation and progression. Evidence suggests that non-stem tumor cells may undergo dedifferentiation to CSCs, and epigenetic regulation of CSCs provides new opportunities for therapeutic interventions.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Review
Biotechnology & Applied Microbiology
Mai Abdel Mouti, Siim Pauklin
Summary: Pancreatic cancer is a challenging disease, with chemotherapy as the standard treatment that may paradoxically lead to chemoresistance. The crosstalk between pancreatic tumor cells and the surrounding stromal microenvironment plays a crucial role in the development of chemoresistance. The involvement of the TGFB1/INHBA signaling network in regulating key mechanisms related to chemoresistance highlights potential targets for therapeutic strategies.
Review
Cell Biology
Chao-Hui Chang, Siim Pauklin
Summary: Pancreatic cancer is a leading cause of cancer-related deaths worldwide due to delayed diagnosis and limited treatments. Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers, with extracellular vesicles playing a crucial role in regulating tumor growth and metastasis. Understanding the factors in EVs derived from pancreatic ductal adenocarcinoma can provide insights into potential early diagnosis and therapeutic strategies against this deadly cancer.
CELL DEATH & DISEASE
(2021)
Review
Oncology
Hannah Pook, Siim Pauklin
Summary: Pancreatic cancer is highly deadly, with current treatments facing various challenges such as late diagnosis, immunologically cold phenotype, and difficulty in distinguishing beneficial drug targets. Recent progress includes identifying mFOLFIRINOX as a standard-of-care adjuvant therapy and discovering KRAS(G12C) mutant inhibitors, with promising new approaches targeting the tumor microenvironment, enhancing immunotherapies, epigenetic modulation, and destruction of CSCs.
Review
Oncology
Linh-Huyen Truong, Siim Pauklin
Summary: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with no effective treatment currently available. The complexity and dynamics of the tumor microenvironment (TME) play a crucial role in PDAC treatment resistance, emphasizing the need for a detailed understanding of the TME. Insights into the heterogeneous TME composition and interplay among its components are essential for developing more efficient therapeutic approaches for PDAC.
Article
Cardiac & Cardiovascular Systems
Yuliang Feng, Liuyang Cai, Wanzi Hong, Chunxiang Zhang, Ning Tan, Mingyang Wang, Cheng Wang, Feng Liu, Xiaohong Wang, Jianyong Ma, Chen Gao, Mohit Kumar, Yuanxi Mo, Qingshan Geng, Changjun Luo, Yan Lin, Haiyang Chen, Shuang-Yin Wang, Michael J. Watson, Anil G. Jegga, Roger A. Pedersen, Ji-Dong Fu, Zhao Wang, Guo-Chang Fan, Sakthivel Sadayappan, Yigang Wang, Siim Pauklin, Feng Huang, Wei Huang, Lei Jiang
Summary: This study investigates the role of 3-dimensional chromatin topology in dilated cardiomyopathy (DCM) by analyzing the epigenome and transcriptome maps of DCM and nonfailing heart tissues. The research reveals that the reprogramming of chromatin topology is associated with transcriptional dysregulation in DCM, with the key transcription factor HAND1 implicated in the process. The findings provide insights into the pathogenesis of DCM and highlight the importance of chromatin organization in heart failure.
Review
Oncology
Siwei Deng, Yuliang Feng, Siim Pauklin
Summary: This review discusses the importance of three-dimensional chromatin structures in biological processes and diseases, as well as the key structural protein elements involved in chromatin interactions. The recent development of technologies and bioinformatics approaches for studying chromatin interactions in gene expression regulation is also summarized.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Letter
Environmental Sciences
Siew Woh Choo, Ju Lian Chong, Philippe Gaubert, Alice Catherine Hughes, Stephen O'Brien, Anne-Lise Chaber, Agostinho Antunes, Sara Platto, Nick Ching-Min Sun, Li Yu, Klaus-Peter Koepfli, Tulshi Laxmi Suwal, Mukesh Thakur, Stephan Ntie, Elisa Panjang, Jayaraj Vijaya Kumaran, Tariq Mahmood, Sean P. Heighton, Dago Dorji, Bi Sery Gonedele, Bryan Raveen Nelson, Chabi A. M. S. Djagoun, Ing Hoe Loh, Prativa Kaspal, Siim Pauklin, Toby Michelena, Hongxiang Zhu, Leonard Lipovich, Xuechen Tian, Siwei Deng, Christopher E. Mason, Jingyang Hu, Robert White, Nicholas S. Jakubovics, Wei Yee Wee, Tze King Tan, Kum Thong Wong, Steve Paterson, Ming Chen, Yixin Zhang, Rofina Yasmin Othman, Larry C. Brown, Bairong Shen, Guanghou Shui, Mia Yang Ang, Yunqi Zhao, Yongming Li, Bo Zhang, Cheng Tung Chong, Yu Meng, Aloysius Wong, Jianzhong Su, Hasmahzaiti Omar, Hua Shen, Choo Hock Tan, Hongyu Xu, Ian C. Paterson, Minyan Wang, Chee-Kai Chan, Siyuan Zhang, Avirup Dutta, Tay Sun Tee, Noel P. D. Juvigny-Khenafou, Naresh V. R. Mutha, Muhamad Afiq Aziz
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Oncology
Egle-Helene Ervin, Rhiannon French, Chao -Hui Chang, Siim Pauklin
Summary: Cell identity is determined by the transcriptional profile, and in cancer, deregulation of transcription factors allows cancer cells to acquire a stem-like state. These stem-like cancer cells are highly metastatic and therapy resistant. This article reviews recent research findings and describes the role of common transcription factors in maintaining the stemness state.
SEMINARS IN CANCER BIOLOGY
(2022)
Editorial Material
Cell Biology
Yingwen Lin, Haifeng Zhang, Hao Chen, Siim Pauklin, Qingchun Zeng
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Pharmacology & Pharmacy
Mai Abdel Mouti, Siim Pauklin
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Mai Abdel Mouti, Siwei Deng, Martin Pook, Jessica Malzahn, Aniko Rendek, Stefania Militi, Reshma Nibhani, Zahir Soonawalla, Udo Oppermann, Chang-il Hwang, Siim Pauklin
Summary: The molecular mechanisms that maintain the characteristics of pancreatic cancer stem cells (PCSCs) are poorly understood. In this study, the authors identify the histone methyltransferase KMT2A as a binding partner of a protein subcomplex, and demonstrate its role as an epigenetic regulator of PCSC properties. Targeting this protein subcomplex has potential therapeutic effects in pancreatic cancer.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Stefania Militi, Reshma Nibhani, Morteza Jalali, Siim Pauklin
Summary: The retinoblastoma family proteins (RBs) and E2F transcription factors not only regulate cell cycle progression but also affect cell fate choices. This study reveals that RBs, especially RBL2/p130, repress WNT ligands to direct ectoderm specification. The cooperation between RBs, E2Fs, and GCN5, as well as the temporal fluctuations of WNT/β-catenin and DLL/NOTCH signaling activity, play a crucial role in neuroepithelial and neural crest specification. This non-cell-autonomous function of RBL2-E2F has significant implications for cell fate specification in stem cells, tissue homeostasis, and tumorigenesis.
Editorial Material
Biotechnology & Applied Microbiology
Shiyi Yu, Guoyong Chen, Siim Pauklin, Yunjiao Zhang, Yuliang Feng, Hao Chen
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
