Article
Genetics & Heredity
Takahiro Sano, Koki Ueda, Keiji Minakawa, Tsutomu Mori, Yuko Hashimoto, Haruhiko Koseki, Yasuchika Takeishi, Kazuhiko Ikeda, Takayuki Ikezoe
Summary: This study generated Uhrf2(-/-) mice to investigate the role of UHRF2 deletion in hematopoiesis. The results showed that the absence of UHRF2 did not affect blood counts, bone marrow findings, and spleen weights. However, the proportions of Uhrf2(-/-) cells were decreased compared to Uhrf2(+/+) cells in competitive repopulation assays, indicating a potential regulatory role of UHRF2 in hematopoiesis.
Article
Cell & Tissue Engineering
Zenghua Lin, Maile K. Hollinger, Zhijie Wu, Wanling Sun, Kaylind Batey, Jisoo Kim, Jichun Chen, Xingmin Feng, Neal S. Young
Summary: It was found that sirolimus enhanced the regeneration of hematopoietic stem and progenitor cells in mice exposed to sublethal total body irradiation and other regenerative stressors. The effects were associated with increased expression of hematopoietic genes, reduced DNA damage and clearance of cellular reactive oxygen species. Sirolimus also showed potential clinical applications for the treatment and prevention of hematopoietic injury.
Article
Multidisciplinary Sciences
Keiyo Takubo, Phyo Wai Htun, Takeshi Ueda, Yasuyuki Sera, Masayuki Iwasaki, Miho Koizumi, Kohei Shiroshita, Hiroshi Kobayashi, Miho Haraguchi, Shintaro Watanuki, Zen-ichiro Honda, Norimasa Yamasaki, Ayako Nakamura- Ishizu, Fumio Arai, Noboru Motoyama, Tomohisa Hatta, Tohru Natsume, Toshio Suda, Hiroaki Honda
Summary: The gene Mbtd1 plays a crucial role in regulating the number and function of hematopoietic stem cells. In mice deficient in Mbtd1, the numbers of stem cells and progenitors increase, and these deficient stem cells exhibit an overactive cell cycle and impaired response to stress. The study also shows that Mbtd1 is directly involved in maintaining cell cycle quiescence by binding to the promoter region of the FoxO3a gene, which is essential for the normal function of hematopoietic stem cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Simranpreet Kaur, Anuj Sehgal, Andy C. Wu, Susan M. Millard, Lena Batoon, Cheyenne J. Sandrock, Michelle Ferrari-Cestari, Jean-Pierre Levesque, David A. Hume, Liza J. Raggatt, Allison R. Pettit
Summary: Treatment with CSF1-Fc in mice led to expansion of macrophages and HSC pool, but did not directly affect CD48(-)CD150(+) HSC. The treatment also increased HSC in the spleen. Pre-treatment with CSF1-Fc improved HSPC mobilization and reconstitution potential after G-CSF treatment.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yan Qi, Shilei Chen, Yukai Lu, Zihao Zhang, Song Wang, Naicheng Chen, Mingqiang Shen, Fang Chen, Mo Chen, Yong Quan, Lijing Yang, Yang Xu, Yongping Su, Mengjia Hu, Junping Wang
Summary: The research demonstrates that grape seed proanthocyanidin extract can ameliorate IR-induced HSPC injury by upregulating the expression of Foxo1 and its target antioxidant genes, thereby reducing ROS production and DNA damage while increasing HSC reconstituting ability and survival in irradiated mice.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell & Tissue Engineering
Jianan Jiang, Jinhua Qin, Jisheng Li, Xiaosong Lin, Bowen Zhang, Zeng Fan, Lijuan He, Quan Zeng, Wen Yue, Min Zheng, Xuetao Pei, Yanhua Li
Summary: This study found that the small molecule Ricolinostat can promote the differentiation of megakaryocytic cells from HSPCs, increase the proliferation of megakaryocytic cells, and decrease the secretion of IL-8 and the expression of CXCR2, thereby improving the efficiency of megakaryocytic differentiation of HSPCs.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Oncology
Makiko Mochizuki-Kashio, Noriko Otsuki, Kota Fujiki, Sherif Abdelhamd, Peter Kurre, Markus Grompe, Atsushi Iwama, Kayoko Saito, Ayako Nakamura-Ishizu
Summary: Fanconi Anemia (FA) is a genetic bone marrow failure disorder commonly diagnosed in school age children. Mitochondrial metabolism and mitophagy play important roles in long-term hematopoietic stem cell (HSC) function. Impaired mitophagy has been observed in FA cells. This study found that replication stress (RS) activates mitochondrial metabolism and mitophagy in HSC, and that FL HSCs deficient in FANCD2 show increased mitochondrial metabolism and mitophagy while adult FANCD2-deficient BM HSCs exhibit decreased mitophagy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Junchen Chen, Xiaoxue Dong, Xuejun Cheng, Qiang Zhu, Jinyu Zhang, Qian Li, Xiaoli Huang, Min Wang, Liping Li, Weixiang Guo, Binggui Sun, Qiang Shu, Wen Yi, Xuekun Li
Summary: Ogt deficiency in adult neural stem/progenitor cells leads to a decrease in the aNSPC pool, abnormal neurogenesis, and impaired cognitive function in adult mice. Mechanistic studies reveal that Ogt catalyzes the O-GlcNAc modification of the Notch TM/ICD fragment, which in turn affects neurogenic defects induced by Ogt deficiency.
Article
Biochemistry & Molecular Biology
You Jung Hwang, Dong-Yeop Shin, Min-Jung Kim, Hyosun Jang, Soyeon Kim, Hyunwon Yang, Won Il Jang, Sunhoo Park, Sehwan Shim, Seung Bum Lee
Summary: This study found that SR1 could alleviate radiation-induced hematopoietic injury. It increased the survival rate and promoted the recovery of peripheral blood cell counts in irradiated mice. In vitro experiments also showed that SR1 increased the population of human hematopoietic stem/progenitor cells, reduced radiation-induced DNA damage and apoptosis. These results suggest that SR1 may be a potential radiomitigator for hematopoietic injury.
Article
Multidisciplinary Sciences
Yohko Kitagawa, Akihiro Ikenaka, Ryohichi Sugimura, Akira Niwa, Megumu K. Saito
Summary: Cell differentiation is achieved through the acquisition of a cell type-specific transcriptional program and epigenetic landscape. Research has shown that the patterning of cell type-specific enhancers occurs before cell fate decisions, but the mechanisms for initiating cell specification and properly restricting differentiation remain unclear. In this study, the activation of hematopoietic enhancers during arterialization of hemogenic endothelium, a key step in hematopoiesis, was observed. It was also found that the transcription factor ZEB2, involved in arterial endothelial cell regulation, and the hematopoietic regulator MEIS1 are independently required for activating these enhancers. Deficiency in ZEB2 or MEIS1 impairs hematopoietic cell development. These findings suggest that multiple regulators expressed during early development contribute non-redundantly to the establishment of the hematopoietic enhancer landscape, thereby restricting cell differentiation despite the unrestricted expression of these regulators in hematopoietic cells.
Article
Multidisciplinary Sciences
Michele C. Buck, Lisa Bast, Judith S. Hecker, Jennifer Riviere, Maja Rothenberg-Thurley, Luisa Vogel, Dantong Wang, Immanuel Andrae, Fabian J. Theis, Florian Bassermann, Klaus H. Metzeler, Robert A. J. Oostendorp, Carsten Marr, Katharina S. Goetze
Summary: Clonal hematopoiesis of indeterminate potential (CHIP) is the acquisition of somatic mutations in hematopoietic stem/progenitor cells (HSPC) leading to clonal blood cell expansion. Computational modeling shows that alternative hierarchies may better describe HSPC kinetics in CHIP and MDS samples compared to the standard hematopoietic hierarchy. The reorganization of the HSPC compartment can already be detected in the premalignant CHIP state.
Article
Immunology
Lifei Hou, Koichi Yuki
Summary: CD11a plays a critical role in leukocyte arrest and immunological synapse formation, but its role in the bone marrow is not well studied. This research showed that CD11a is expressed on all subsets of hematopoietic stem and progenitor cells (HPSCs). CD11a deficiency enhances HSPCs activity under LPS stimulation, possibly by upregulating the production of IL-27 to promote cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yuko Tadokoro, Atsushi Hirao
Summary: This review examines the regulation of nutrient-driven metabolism in hematopoietic stem cells (HSCs) from two perspectives - intracellular metabolism and dietary intake of nutrients. It highlights the importance of catabolic regulators in maintaining stem cell homeostasis and the impact of dietary changes on stem cell behavior. Understanding these processes may lead to new avenues of medical research and improvements in human health care.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Wenjing Li, Haiwei Liang, Yanxiao Ao, Baixue Tang, Junyang Li, Ning Li, Jianwei Wang, Yanan Du
Summary: Hematopoietic stem cells (HSCs) have the ability to differentiate into all blood cells and immune cells. By simulating the bone marrow microenvironment, we designed degradable scaffolds to regulate the fate of HSCs. In vivo transplantation confirmed the importance of the scaffolds in maintaining hematopoietic function, providing a foundation for parameter design in 3D HSC culture systems.
Article
Urology & Nephrology
Steicy Sobrino, Chrystelle Abdo, Benedicte Neven, Adeline Denis, Nathalie Gouge-Biebuyck, Emmanuel Clave, Soeli Charbonnier, Tifanie Blein, Camille Kergaravat, Marion Alcantara, Patrick Villarese, Romain Berthaud, Laurene Dehoux, Souha Albinni, Esma Karkeni, Chantal Lagresle-Peyrou, Marina Cavazzana, Remi Salomon, Isabelle Andre, Antoine Toubert, Vahid Asnafi, Capucine Picard, Stephane Blanche, Elizabeth Macintyre, Olivia Boyer, Emmanuell Six, Julien Zuber
Summary: Long-term multilineage hematopoietic donor chimerism can occur in patients who receive a transplanted solid organ with lymphoid tissues, such as the intestine or liver. However, there is currently no evidence for kidney-resident hematopoietic stem cells in any mammal species. In this study, we found that human kidney-derived hematopoietic stem cells can reside in the recipient's bone marrow and replace host counterparts, leading to full donor chimerism of both lymphoid and myeloid lineages.
KIDNEY INTERNATIONAL
(2023)
Article
Biotechnology & Applied Microbiology
Qing-Shuo Zhang, Amita Tiyaboonchai, Sean Nygaard, Kevin Baradar, Angela Major, Niveditha Balaji, Markus Grompe
Summary: Enhancing the efficiency of gene repair by homologous recombination in the liver can be achieved through CRISP/Cas9 incision near the mutation site. Interventions to further improve in vivo hepatocyte gene repair include inducing cell division with thyroid hormone T3 in neonatal mice and investigating the importance of the Fanconi anemia DNA repair pathway in hepatocyte gene repair.
HUMAN GENE THERAPY
(2021)
Article
Cell & Tissue Engineering
Alfredo Rodriguez, Kaiyang Zhang, Anniina Farkkila, Jessica Filiatrault, Chunyu Yang, Martha Velazquez, Elissa Furutani, Devorah C. Goldman, Benilde Garcia de Teresa, Gilda Garza-Mayen, Kelsey McQueen, Larissa A. Sambel, Bertha Molina, Leda Torres, Marisol Gonzalez, Eduardo Vadillo, Rosana Pelayo, William H. Fleming, Markus Grompe, Akiko Shimamura, Sampsa Hautaniemi, Joel Greenberger, Sara Frias, Kalindi Parmar, Alan D. D'Andrea
Summary: The overexpression of MYC in Fanconi anemia (FA) patients leads to dysfunction of hematopoietic stem and progenitor cells (HSPCs) and increased DNA damage. MYC-high HSPCs exhibit a significant downregulation of cell adhesion genes, facilitating the egress of HSPCs from bone marrow to peripheral blood.
Article
Biotechnology & Applied Microbiology
Dhwanil A. Dalwadi, Laura Torrens, Jordi Abril-Fornaguera, Roser Pinyol, Catherine Willoughby, Jeffrey Posey, Josep M. Llovet, Christian Lanciault, David W. Russell, Markus Grompe, Willscott E. Naugler
Summary: Integration of adeno-associated virus (AAV) into host genomes can lead to hepatocellular carcinoma (HCC), especially when it occurs in oncogenic hotspots. Research has shown that mice exposed to rAAV gene therapy in the context of non-alcoholic fatty liver disease (NAFLD) are more likely to develop HCC, highlighting the potential risk factors associated with rAAV-induced oncogenesis.
Article
Hematology
Alfredo Rodriguez, Chunyu Yang, Elissa Furutani, Benilde Garcia de Teresa, Martha Velazquez, Jessica Filiatrault, Larissa A. Sambel, Tin Phan, Patricia Flores-Guzman, Silvia Sanchez, Angelica Monsivais Orozco, Hector Mayani, Ozge V. Bolukbasi, Anniina Farkkila, Michael Epperly, Joel Greenberger, Akiko Shimamura, Sara Frias, Markus Grompe, Kalindi Parmar, Alan D. D'Andrea
Summary: Fanconi anemia (FA) is a chromosome instability syndrome with congenital abnormalities, cancer predisposition, and bone marrow failure (BMF). AVID200, a TGF beta 1- and TGF beta 3-specific inhibitor, shows promising effects on FA hematopoiesis, particularly in patients progressing to severe aplastic anemia or myelodysplastic syndrome (MDS). AVID200 downregulates NHEJ-related genes and reduces DNA damage in primary FA HSPCs, indicating its potential as a therapeutic approach for improving BMF in FA.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Allyson J. Merrell, Tao Peng, Jinyang Li, Kathryn Sun, Bin Li, Takeshi Katsuda, Markus Grompe, Kai Tan, Ben Z. Stanger
Summary: Hepatocytes undergo extensive chromatin and transcriptional changes during biliary reprogramming, resulting in altered gene expression profiles including robust induction of biliary genes and weaker repression of hepatocyte genes. Single-cell analysis revealed that Smad4 mutation can significantly increase reprogramming.
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
Medicine, Research & Experimental
Laura I. Marquez Loza, Ashley L. Cooney, Qian Dong, Christoph O. Randak, Stefano Rivella, Patrick L. Sinn, Paul B. McCray
Summary: This study investigated promoter choice and CFTR codon optimization as strategies to regulate CFTR expression. The results showed that EF1 alpha produced greater currents than PGK, and identified a coCFTR sequence that conferred significantly increased functional CFTR expression. Optimal promoter and CFTR sequences advance lentiviral vectors towards CF gene therapy clinical trials.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Mina Ogawa, Jia-Xin Jiang, Sunny Xia, Donghe Yang, Avrilynn Ding, Onofrio Laselva, Marcela Hernandez, Changyi Cui, Yuichiro Higuchi, Hiroshi Suemizu, Craig Dorrell, Markus Grompe, Christine E. Bear, Shinichiro Ogawa
Summary: The study identifies key pathways regulating cholangiocyte maturation and successfully generates functional cholangiocytes with mature characteristics, enhancing their potential for therapeutic applications in biliary diseases.
NATURE COMMUNICATIONS
(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
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)
