Editorial Material
Oncology
Eunmi Lee, Yibin Kang
Summary: The combination of single-cell lineage tracing and RNA sequencing has opened up unprecedented opportunities for prospectively exploring metastatic dynamics. In a pancreatic cancer model, Simeonov et al. developed the macsGESTALT lineage recording system, revealing that hybrid EMT states and S100 expression are associated with increased metastatic abilities.
Article
Cell & Tissue Engineering
Panagiota Siatra, Giannis Vatsellas, Athanasia Chatzianastasiou, Evangelos Balafas, Theodora Manolakou, Andreas Papapetropoulos, Anna Agapaki, Eleni-Taxiarchia Mouchtouri, Prashant J. Ruchaya, Artemis G. Korovesi, Manolis Mavroidis, Dimitrios Thanos, Dimitris Beis, Ioannis Kokkinopoulos
Summary: Heart transplantation is the only cure for patients with heart failure, but it is limited by donor shortage, immunosuppression and economic costs. Therefore, there is an urgent need to identify cell populations capable of cardiac regeneration. Recent studies have identified a Tbx5-expressing precursor cell population in the injured adult mammalian heart that shows potential for cardiomyocyte regeneration.
NPJ REGENERATIVE MEDICINE
(2023)
Review
Cell Biology
Toshihiro Mitaka, Norihisa Ichinohe, Naoki Tanimizu
Summary: Mature hepatocytes in the liver can be categorized into three subpopulations based on their proliferative capability: type I, type II, and type III cells. Small hepatocytes (SHs) are unique cells that appear in the liver and may play a role in liver regeneration. They can be derived from hepatocytic progenitors and are involved in the liver's development and growth.
Article
Multidisciplinary Sciences
Lingjuan He, Wenjuan Pu, Xiuxiu Liu, Zhenqian Zhang, Maoying Han, Yi Li, Xiuzhen Huang, Ximeng Han, Yan Li, Kuo Liu, Mengyang Shi, Liang Lai, Ruilin Sun, Qing-Dong Wang, Yong Ji, Jan S. Tchorz, Bin Zhou
Summary: A genetic system called ProTracer was developed to record proliferation events of entire cell populations, revealing more hepatocyte proliferation in distinct zones in the liver. This unbiased method enables the detection of specific cellular compartments with enhanced regenerative capacities.
Article
Biochemistry & Molecular Biology
Shudong Niu, Kaixin Cheng, Longzhong Jia, Jing Liang, Lu Mu, Yibo Wang, Xuebing Yang, Chen Yang, Yan Zhang, Chao Wang, Lijun Huang, Huarong Wang, Shuang Zhang, Hua Zhang
Summary: This study demonstrated that ovarian granulosa cell tumors (GCTs) originate from mutant granulosa cells (GCs) and identified the upregulation of immune evasion genes Cd24a and Cd47 as a mechanism for the transition of mutant GCs to GCTs. Treatment with the Cd47 inhibitor RRX-001 effectively suppressed GCT growth in vivo.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Physiology
Wenzheng Zhang, Chao Gao, Akaki Tsilosani, Rohan Samarakoon, Robert Plews, Paul J. Higgins
Summary: This article summarizes the recent advances in utilizing the Cre-LoxP system for tracking stem/progenitor cells in kidney development and maturity, as well as the development and characterization of various Cre drivers.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Cell & Tissue Engineering
Shun He, Zhihou Guo, Mingshan Zhou, Haichang Wang, Zhuonan Zhang, Mengyang Shi, Xufeng Li, Xueying Yang, Lingjuan He
Summary: In this study, the authors used a proliferation recording system called ProTracer to investigate the spatial-temporal proliferation of hepatocytes during pregnancy. They found that hepatocyte proliferation during pregnancy starts in zone 1, then progresses to zone 2, and finally to zone 3, with the majority of new hepatocytes being generated in zone 2. Single-cell RNA sequencing analysis showed that Ccnd1 is highly enriched in zone 2 hepatocytes. Further experiments using genetic lineage tracing revealed that Ccnd1+ hepatocytes preferentially expand during pregnancy. Additionally, the authors demonstrated that estrogen-induced liver enlargement during pregnancy is dependent on Ccnd1. Overall, this study uncovers a unique spatial-temporal pattern of hepatocyte proliferation during pregnancy, with zone 2 Ccnd1+ hepatocytes being the major cellular source for hepatic enlargement.
Article
Biochemistry & Molecular Biology
Lei-Lei Wang, Carolina Serrano, Xiaoling Zhong, Shuaipeng Ma, Yuhua Zou, Chun-Li Zhang
Summary: Recent studies have shown that in vivo cell fate conversions may not actually be converting astrocytes into neurons, but instead utilizing endogenous neurons. Lineage tracing strategies are necessary to accurately track the origin of converted cells, highlighting the importance of applying stringent tracing techniques in studies of cell fate conversions in vivo.
Article
Biochemistry & Molecular Biology
Dian Yang, Matthew G. Jones, Santiago Naranjo, William M. Rideout III, Kyung Hoi (Joseph) Min, Raymond Ho, Wei Wu, Joseph M. Replogle, Jennifer L. Page, Jeffrey J. Quinn, Felix Horns, Xiaojie Qiu, Michael Z. Chen, William A. Freed-Pastor, Christopher S. McGinnis, David M. Patterson, Zev J. Gartner, Eric D. Chow, Trever G. Bivona, Michelle M. Chan, Nir Yosef, Tyler Jacks, Jonathan S. Weissman
Summary: Tumor evolution is driven by progressive genetic and epigenetic alterations, enabling unrestricted growth and expansion. This study provides insights into the hierarchical nature of tumor evolution through tracking phylogenetic relationships between cancer cells, allowing for in-depth studies of tumor progression.
Review
Gastroenterology & Hepatology
Patrick D. Wilkinson, Andrew W. Duncan
Summary: Hepatocytes are the primary functional cells of the liver, playing essential roles in homeostasis, regeneration, and injury. They can be classified into diploid and polyploid cells, each with specialized functions in accelerating liver regeneration and protecting against tumor initiation and chronic injury.
SEMINARS IN LIVER DISEASE
(2021)
Editorial Material
Parasitology
Anita A. Koshy
Summary: Researchers generated a stable, complex population of Toxoplasma gondii using the CRISPR/Cas9 method and found that the pathway to infect the brain is widely permissive, contrary to expectations.
TRENDS IN PARASITOLOGY
(2022)
Article
Immunology
Jue Feng, Joseph N. Pucella, Geunhyo Jang, Marcela Alcantara-Hernandez, Samik Upadhaya, Nicholas M. Adams, Alireza Khodadadi-Jamayran, Colleen M. Lau, Marlon Stoeckius, Stephanie Hao, Peter Smibert, Aristotelis Tsirigos, Juliana Idoyaga, Boris Reizis
Summary: This study investigates the developmental origins of dendritic cells (DCs) and reveals the shared origin of pDCs and cDCs, suggesting a revised scheme of DC development.
Article
Cardiac & Cardiovascular Systems
Tea Kocijan, Michael Rehman, Andrea Colliva, Elena Groppa, Matteo Leban, Simone Vodret, Nina Volf, Gabriele Zucca, Ambra Cappelletto, Giulia Maria Piperno, Lorena Zentilin, Mauro Giacca, Federica Benvenuti, Bin Zhou, Ralf H. Adams, Serena Zacchigna
Summary: Cardiac ischemia does not effectively induce angiogenesis, leading to cardiomyocyte death and loss of function. Clinical trials attempting to induce therapeutic revascularization through pro-angiogenic molecule delivery have failed, indicating poor angiogenic response in cardiac endothelial cells.
CARDIOVASCULAR RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Huaizhou Jiang, Veronica Garcia, Jennifer Abla Yanum, Joonyong Lee, Guoli Dai
Summary: During liver regeneration, Bmal1 partially modulates the oscillation of S-phase progression, fully controls the rhythmicity of M-phase advancement, and largely governs fluctuations in fat metabolism in replicating hepatocytes. Additionally, Bmal1 plays these roles by ensuring formation of expression peaks of cell cycle components and regulators, as well as timing and levels of activation of mitogenic signaling molecules, leading to an oxidative stress state in regenerated liver tissue.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Joaquim Javary, Nathalie Allain, Zakaria Ezzoukhry, Sylvaine Di Tommaso, Jean-William Dupuy, Pierre Costet, Nathalie Dugot-Senant, Frederic Saltel, Violaine Moreau, Pierre Dubus, Samira Benhamouche-Trouillet
Summary: Previous studies have shown that Reptin is crucial for hepatocyte proliferation in vivo and liver regeneration, as observed in the Reptin(LKO) mouse model. The impaired liver regeneration in Reptin(LKO) mice post partial hepatectomy is associated with decreased cyclin-A expression and mTORC1 and MAPK signaling. The progressive loss of Reptin invalidation in the model leads to atypical liver regeneration, with hypertrophic and proliferative hepatocytes replacing hypotrophic ones.
LIVER INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Tomonori Matsumoto, Leslie Wakefield, Alexander Peters, Myron Peto, Paul Spellman, Markus Grompe
Summary: Polyploidy is common in cancer and normal tissues, with polyploid hepatocytes proliferating and reducing ploidy during liver regeneration. Research shows that polyploid hepatocytes easily form liver tumors through frequent ploidy reduction, which is an early step in liver tumorigenesis.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Dhwanil A. Dalwadi, Andrea Calabria, Amita Tiyaboonchai, Jeffrey Posey, Willscott E. Naugler, Eugenio Montini, Markus Grompe
Summary: Research found a high frequency of chromosomal integrations of recombinant adeno-associated viral vectors in liver cells, with most inserted sequences heavily rearranged and accompanied by deletions of host genomic sequences at integration sites. This indicates a certain risk associated with rAAV integration.
Article
Cell Biology
Anne Vonada, Amita Tiyaboonchai, Sean Nygaard, Jeffrey Posey, Alexander Mack Peters, Shelley R. Winn, Alessio Cantore, Luigi Naldini, Cary O. Harding, Markus Grompe
Summary: The study demonstrates that therapeutic modified hepatocytes can be efficiently selected in preclinical models by using mildly hepatotoxic acetaminophen, leading to significant expansion of transgene-bearing hepatocytes and reaching therapeutic thresholds in genetic liver diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Cell & Tissue Engineering
Bin Li, Yuhan Wang, Carl Pelz, Josh Moss, Ruth Shemer, Yuval Dor, Yassmine K. Akkari, Pamela S. Canady, Willscott E. Naugler, Susan Orloff, Markus Grompe
Summary: By inhibiting specific pathways, human cirrhotic liver epithelial cells can be expanded in vitro and exhibit high proliferative capacity, with gene expression and DNA methylation analysis showing an intermediate state. Compared to their murine counterparts, human-derived liver cells have limited redifferentiation potential.
STEM CELL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Sunghee Chai, Youngjin Kim, Feorillo Galivo, Craig Dorrell, Leslie Wakefield, Jeffrey Posey, Amanda M. Ackermann, Klaus H. Kaestner, Matthias Hebrok, Markus Grompe
Summary: This study successfully achieved specific expression of transgenes in human beta cells by designing recombinant adeno-associated virus vectors. Specific expression was achieved by combining two regulatory elements, a promoter consisting of two INS and miRNA recognition elements. This method reduces nonspecific transgene expression and is of great significance for the treatment of diabetes.
HUMAN GENE THERAPY
(2022)
Article
Hematology
Jessica A. Pollard, Elissa Furutani, Shanshan Liu, Erica Esrick, Laurie E. Cohen, Jacob Bledsoe, Chih-Wei Liu, Kun Lu, Maria Jose Ramirez de Haro, Jordi Sumalles, Maggie Malsch, Ashley Kuniholm, Ashley Galvin, Myriam Armant, Annette S. Kim, Kaitlyn Ballotti, Lisa Moreau, Yu Zhou, Daria Babushok, Farid Boulad, Clint Carroll, Helge Hartung, Amy Hont, Taizo Nakano, Tim Olson, Sei-Gyung Sze, Alexis A. Thompson, Marcin W. Wlodarski, Xuesong Gu, Towia A. Libermann, Alan D'Andrea, Markus Grompe, Edie Weller, Akiko Shimamura
Summary: This study investigated the feasibility and tolerability of metformin treatment in patients with Fanconi anemia (FA). The results showed that metformin is safe and tolerable in nondiabetic patients with FA and may provide therapeutic benefits.
Article
Gastroenterology & Hepatology
Takeshi Katsuda, Hector Cure, Jonathan Sussman, Kamen P. Simeonov, Christopher Krapp, Zoltan Arany, Markus Grompe, Ben Z. Stanger
Summary: This study introduces a rapid in vivo multiplexed editing (RIME) method that enables the efficient inactivation of one or more genes in the mouse liver. The method is quick, efficient, and cost-effective, making it a valuable tool for analyzing multiple genes in vivo.
Article
Gastroenterology & Hepatology
Branden D. Tarlow, W. Ray Kim, Ajitha Mannalithara, Paul Y. Kwo, C. Andrew Bonham, Allison Kwong
Summary: This study found that MELD 3.0 scores beyond 40 are associated with increasing waitlist mortality without adversely affecting posttransplant outcomes. Uncapping the MELD score for waitlist candidates may lead to greater survival benefits from liver transplantation.
Review
Biochemistry & Molecular Biology
Tomonori Matsumoto
Summary: Hepatocytes are polyploid cells that can proliferate and divide, playing a crucial role in maintaining liver homeostasis and regeneration. Alterations in hepatocyte ploidy are implicated in the pathogenesis of liver cirrhosis and cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Netanel Loyfer, Judith Magenheim, Ayelet Peretz, Gordon Cann, Joerg Bredno, Agnes Klochendler, Ilana Fox-Fisher, Sapir Shabi-Porat, Merav Hecht, Tsuria Pelet, Joshua Moss, Zeina Drawshy, Hamed Amini, Patriss Moradi, Sudharani Nagaraju, Dvora Bauman, David Shveiky, Shay Porat, Uri Dior, Gurion Rivkin, Omer Or, Nir Hirshoren, Einat Carmon, Alon Pikarsky, Abed Khalaileh, Gideon Zamir, Ronit Grinbaum, Machmud Abu Gazala, Ido Mizrahi, Noam Shussman, Amit Korach, Ori Wald, Uzi Izhar, Eldad Erez, Vladimir Yutkin, Yaacov Samet, Devorah Rotnemer Golinkin, Kirsty L. Spalding, Henrik Druid, Peter Arner, A. M. James Shapiro, Markus Grompe, Alex Aravanis, Oliver Venn, Arash Jamshidi, Ruth Shemer, Yuval Dor, Benjamin Glaser, Tommy Kaplan
Summary: DNA methylation is an important epigenetic mark that regulates gene expression and chromatin organization. This study presents a human methylome atlas based on deep whole-genome bisulfite sequencing, providing a comprehensive analysis of 39 cell types from 205 healthy tissue samples. The atlas reveals tissue-specific methylation patterns and potential biomarkers for liquid biopsies.
Article
Multidisciplinary Sciences
Amita Tiyaboonchai, Anne Vonada, Jeffrey Posey, Carl Pelz, Leslie Wakefield, Markus Grompe
Summary: This study uses self-cleaving gRNAs to create drug-selectable gene editing events in specific hepatocyte loci, resulting in expanded gene-edited cells and therapeutic levels of gene expression.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Hiep Tai Nguyen, Weiliang Tang, Andrew L. H. Webster, Jeffrey R. R. Whiteaker, Christopher M. M. Chandler, Ricardo Errazquin, Khashayar Roohollahi, Madeline Fritzke, Elizabeth E. E. Hoskins, Erica Jonlin, Leslie Wakefield, Lucas B. B. Sullivan, Eleanor Y. Y. Chen, Josephine Dorsman, Ruud Brakenhoff, Amanda G. G. Paulovich, Markus Grompe, Ramon Garcia-Escudero, Susanne I. I. Wells, Agata Smogorzewska, Raymond J. J. Monnat Jr
Summary: Fanconi anemia (FA) is a heritable syndrome associated with high risk of squamous carcinomas, and the origins of these carcinomas are not well understood. The Fanconi Anemia Cancer Cell Line Resource (FA-CCLR) was developed to support research on the origins, treatment and prevention of FA-associated carcinomas.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Developmental Biology
Amita Tiyaboonchai, Leslie Wakefield, Anne Vonada, Catherine L. May, Craig Dorrell, David Enicks, Anusha Sairavi, Klaus H. Kaestner, Markus Grompe
Summary: The current gold-standard for genetic lineage tracing in transgenic mice is based on cell-type specific expression of Cre recombinase. As an alternative, we developed a cell-type specific CRISPR/spCas9 system for lineage tracing. This method relies on RNA polymerase II promoter driven self-cleaving guide RNAs (scgRNA) to achieve tissue-specificity. The use of RNA polymerase II promoter driven scgRNAs enables the use of CRISPR/spCas9 for genetic lineage tracing.
DEVELOPMENTAL BIOLOGY
(2023)