Review
Cell Biology
Haofei Wang, Yuchen Yang, Jiandong Liu, Li Qian
Summary: Direct reprogramming converts cells from one lineage into another without going through a pluripotent state, and it is a promising strategy for generating functional cells for therapeutic purposes. Recent advancements include using defined factors for lineage conversion, enhancing reprogrammed cell maturation, and addressing challenges in in vivo direct reprogramming for translational applications.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Review
Cell & Tissue Engineering
Marta Roccio
Summary: Hearing loss is commonly caused by the loss or malfunction of cells in the cochlea, which cannot be reversed in mammals. Studying gene and cellular functions in different animal models helps identify disease causes and potential targets for hearing restoration. Stem cell technologies have allowed the generation of human sensory cell types in vitro, offering new tools for studying human inner ear biology, modeling disease, and validating therapeutics.
Article
Chemistry, Multidisciplinary
Letao Yang, Brian M. Conley, Christopher Rathnam, Hyeon-Yeol Cho, Thanapat Pongkulapa, Brandon Conklin, Ki-Bum Lee
Summary: This study reports the development of a dynamic laser interference lithography (DIL) technique to generate large-scale combinatorial biophysical cue (CBC) arrays with diverse micro/nanostructures for investigating the role of biophysical cues in direct cell reprogramming. Through this approach, unconventional nanopatterns that induce the direct reprogramming of human fibroblasts into neurons were rapidly identified.
Article
Immunology
Olga Zimmermannova, Alexandra G. Ferreira, Ervin Ascic, Marta Velasco Santiago, Ilia Kurochkin, Morten Hansen, Ozcan Met, Ines Caiado, Ilja E. Shapiro, Justine Michaux, Marion Humbert, Diego Soto-Cabrera, Hreinn Benonisson, Rita Silverio-Alves, David Gomez-Jimenez, Carina Bernardo, Monika Bauden, Roland Andersson, Mattias Hoglund, Kenichi Miharada, Yukio Nakamura, Stephanie Hugues, Lennart Greiff, Malin Lindstedt, Fabio F. Rosa, Cristiana F. Pires, Michal Bassani-Sternberg, Inge Marie Svane, Carlos-Filipe Pereira
Summary: Decreased antigen presentation allows cancer cells to escape from the immune system. Researchers successfully reprogrammed cancer cells into professional antigen-presenting cells (APCs) using the gene regulatory network of type 1 conventional dendritic cells (cDC1). This reprogramming restored the expression of antigen presentation complexes and costimulatory molecules, enabling the cancer cells to present tumor antigens and activate CD8(+) T cells for targeted killing. The reprogrammed tumor-APCs also showed impaired tumorigenicity and elicited synergistic antitumor immune responses with immune checkpoint inhibitors.
SCIENCE IMMUNOLOGY
(2023)
Review
Cell Biology
Lakshmy Vasan, Eunjee Park, Luke Ajay David, Taylor Fleming, Carol Schuurmans
Summary: Direct neuronal reprogramming is an innovative technology that converts somatic cells into induced neurons without passing through a pluripotent state. The capacity to create new neurons in the brain has opened up possibilities for treating incurable neurodegenerative diseases and brain injuries. By identifying intrinsic and extrinsic cues, developmental biologists have paved the way for this field, leading to the development of new methodologies for neuronal reprogramming.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bob A. Hersbach, David S. Fischer, Giacomo Masserdotti, Deeksha, Karolina Mojzisova, Thomas Waltzhoeni, Diego Rodriguez-Terrones, Matthias Heinig, Fabian J. Theis, Magdalena Goetz, Stefan H. Stricker
Summary: Collide-seq, a single-cell protocol, has shed light on the basic principles of fate erasure and cell identity conflict resolution in direct reprogramming. It revealed the lack of a common mechanism for the loss of fibroblast-specific gene expression and showed that the abrupt transcriptional changes in converting cells occur when critical levels of reprogramming factors are reached. The study also demonstrated that reprogramming factors can disturb cell identity programs independent of their ability to bind their target genes.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Review
Clinical Neurology
Yuan Yuan Zheng, Hui Xu, Yue Si Wang
Summary: Parkinson's disease is a neurodegenerative disease for which current drug and surgical treatments are not curative and are associated with high risks. Recent advances in cell reprogramming offer new prospects for Parkinson's disease treatment, including the creation of iPSCs, iDNs, and iNSCs. However, this article highlights the limitations of using iPSCs and iNSCs for Parkinson's disease treatment and explores the potential of directly reprogramming somatic cells into iDNs.
NEUROLOGICAL SCIENCES
(2023)
Article
Biology
Marta Fontcuberta-PiSunyer, Ainhoa Garcia-Alaman, Elia Prades, Noelia Tellez, Hugo Alves-Figueiredo, Mireia Ramos-Rodriguez, Carlos Enrich, Rebeca Fernandez-Ruiz, Sara Cervantes, Laura Clua, Javier Ramon-Azcon, Christophe Broca, Anne Wojtusciszyn, Nuria Montserrat, Lorenzo Pasquali, Anna Novials, Joan-Marc Servitja, Josep Vidal, Ramon Gomis, Rosa Gasa
Summary: In this study, human foreskin fibroblasts were directly reprogrammed into insulin-producing cells using 5 pancreatic transcription factors, without pluripotency induction. The reprogrammed cells exhibited beta-cell features and showed glucose-induced insulin secretion, demonstrating the feasibility of generating insulin-producing cells from human fibroblasts via transcription factor-mediated direct reprogramming.
COMMUNICATIONS BIOLOGY
(2023)
Review
Cell Biology
Rachel Dennison, Esteban Usuga, Harriet Chen, Jacob Z. Paul, Christian A. Arbelaez, Yang D. Teng
Summary: In order to facilitate recovery and advance fundamental biology in the brain and spinal cord, researchers are exploring the potential strategy of directly reprogramming or converting astrocytes into neurons (AtN). However, this approach has raised many new questions and alternative explanations, requiring a more in-depth exploration of the mechanisms of the transformation process.
Article
Cell & Tissue Engineering
Kenji Kamimoto, Mohd Tayyab Adil, Kunal Jindal, Christy M. Hoffmann, Wenjun Kong, Xue Yang, Samantha A. Morris
Summary: In direct lineage conversion, TF overexpression reconfigures GRNs to reprogram cell identity. CellOracle is a computational method to infer GRNs from single-cell data, and enables in silico interrogation of network reconfiguration. By combining CellOracle analysis with lineage tracing, we reveal distinct network configurations underlying successful and failed reprogramming, and identify new factors for successful fate conversion.
Article
Cell Biology
Jun Li, Yunfei Bai, Yang Liu, Zhongya Song, Yong Yang, Yang Zhao
Summary: A study found that CDK8 inhibition is necessary for chemically induced cell-fate reprogramming from fibroblasts, suggesting its role as a general molecular barrier in multiple cell reprogramming processes. CDK8 inhibition downregulates proinflammatory pathways and facilitates the induction of a multi-lineage priming state, enhancing fibroblast plasticity. Additionally, CDK8 inhibition promotes fibroblast conversion into hepatocyte-like cells and adipocytes.
Article
Cell & Tissue Engineering
Jinhua Qin, Jian Zhang, Jianan Jiang, Bowen Zhang, Jisheng Li, Xiaosong Lin, Sihan Wang, Meiqi Zhu, Zeng Fan, Yang Lv, Lijuan He, Lin Chen, Wen Yue, Yanhua Li, Xuetao Pei
Summary: A combination of four small molecules has been found to successfully convert human cord blood erythroblasts into induced megakaryocytes (iMKs) that can produce functional platelets, providing a simple and efficient approach for clinical applications.
Article
Cell & Tissue Engineering
Henrik Ahlenius
Summary: Cellular reprogramming is an established discipline that involves converting somatic cells into different cell types for various applications and research purposes, such as disease modeling, cell replacement therapy, regenerative medicine, and immunotherapy.
CELLULAR REPROGRAMMING
(2022)
Review
Biochemistry & Molecular Biology
Dongwei Li, Xiaodong Shu, Ping Zhu, Duanqing Pei
Summary: Recent research has shown that chromatin dynamics are closely linked to cell fate control, with a binary off/on switch occurring during iPSC reprogramming. This implies that similar mechanisms may also be present in normal development, suggesting potential for further approaches to directing cell fate changes.
Article
Biotechnology & Applied Microbiology
Kei Nakai, Kenta Yamamoto, Tsunao Kishida, Shin-ichiro Kotani, Yoshiki Sato, Satoshi Horiguchi, Hironaka Yamanobe, Tetsuya Adachi, Francesco Boschetto, Elia Marin, Wenliang Zhu, Kazunari Akiyoshi, Toshiro Yamamoto, Narisato Kanamura, Giuseppe Pezzotti, Osam Mazda
Summary: Human dermal fibroblasts were successfully converted into osteoblasts using an ALK inhibitor II on FD-NanoClip polysaccharide sheets or fibers, which showed higher calcium deposition compared to control cells. The study suggests that FD-NanoClip may offer a simplified transplantation procedure for repairing large bone defects with better osteogenic outcomes than conventional atelocollagen scaffolding.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Engineering, Biomedical
Masashi Yamanami, Keiichi Kanda, Takanori Kawasaki, Daisuke Kami, Taiji Watanabe, Satoshi Gojo, Hitoshi Yaku
Article
Cell Biology
Hideki Maeda, Daisuke Kami, Ryotaro Maeda, Yuki Murata, Jun-ichiro Jo, Tomoya Kitani, Yasuhiko Tabata, Satoaki Matoba, Satoshi Gojo
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Daisuke Kami, Satoshi Gojo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Multidisciplinary Sciences
Ryotaro Maeda, Daisuke Kami, Hideki Maeda, Akira Shikuma, Satoshi Gojo
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Tomoya Inoue, Keiichi Kanda, Masashi Yamanami, Daisuke Kami, Satoshi Gojo, Hitoshi Yaku
Summary: The study compared the effects of short-duration chemical treatments on the mechanical properties of tissue-engineered vascular grafts constructed in vivo, finding that ET and GA treatment could enhance the mechanical properties without interfering with histological responses.
Article
Cell Biology
Ryotaro Maeda, Daisuke Kami, Akira Shikuma, Yosuke Suzuki, Toshihiko Taya, Satoaki Matoba, Satoshi Gojo
Summary: The RNA decay pathway plays a crucial role in regulating cell identities and differentiation processes by controlling RNA stability in differentiation. Ddx6 and 4E-T co-participate in adipogenesis by maintaining the process and stability of differentiation.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Hideki Maeda, Daisuke Kami, Ryotaro Maeda, Akira Shikuma, Satoshi Gojo
Summary: The research presents a method to treat mitochondrial diseases by replacing mitochondrial DNA, demonstrating its ability to reverse certain genetic diseases and extend the lifespan of patient cells. Mitochondrial DNA-replaced cells could potentially serve as a resource for transplantation to address maternally inherited mitochondrial diseases.
SCIENTIFIC REPORTS
(2021)
Article
Engineering, Biomedical
Masashi Yamanami, Keiichi Kanda, Kazuki Morimoto, Tomoya Inoue, Taiji Watanabe, Osamu Sakai, Daisuke Kami, Satoshi Gojo, Hitoshi Yaku
Summary: The study successfully fabricated allogeneic cardiovascular grafts in animals by implanting silicone rod molds into subcutaneous pouches in dogs and processing the tubular connective tissues. The implanted grafts showed good biocompatibility and endothelial lining, indicating their potential for future clinical applications.
Article
Immunology
Akira Shikuma, Daisuke Kami, Ryotaro Maeda, Yosuke Suzuki, Arata Sano, Toshihiko Taya, Takehiro Ogata, Anne Konkel, Satoaki Matoba, Wolf-Hagen Schunck, Satoshi Gojo
Summary: EEQ-A exhibits potent anti-inflammatory and immunomodulatory properties, improving survival rate and reducing organ damage in sepsis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Daisuke Kami, Toshimasa Ishizaki, Toshihiko Taya, Akira Katoh, Hiroyuki Kouji, Satoshi Gojo
Summary: In cells, mRNA synthesis and decay are influenced by each other, and their balance is altered by external or internal cues, resulting in changes in cell dynamics. It is important to degrade a group of mRNAs that shape a phenotype before cellular transitions. A compound called IAMC-00192 was discovered as a lead compound, which inhibits the interaction between DDX6 and 4E-T proteins and suppresses cellular transitions such as adipogenesis and epithelial-mesenchymal transition (EMT). This inhibitor may have potential as a drug for RNA decay inhibition.
CELL DEATH DISCOVERY
(2022)
Article
Immunology
Yosuke Suzuki, Daisuke Kami, Toshihiko Taya, Arata Sano, Takehiro Ogata, Satoaki Matoba, Satoshi Gojo
Summary: Despite the development of antimicrobial agents and elaborate strategies, polymicrobial sepsis still has a high mortality rate. Mitochondrial dysfunction serves as the basis of pathogenesis. This study investigated the efficacy of a PGC1 alpha agonist called ZLN005 and found that it significantly improved overall survival in an animal model of sepsis. The mechanism of action involved enhanced mitochondrial respiratory capacity, increased function of TFEB, and improved physical contact between mitochondria and lysosomes. ZLN005 supported immune defense by increasing lysosome volume and acidity, resulting in a significant reduction in bacterial load.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Hiroki Kawano, Yuko Kawano, Chen Yu, Mark W. LaMere, Matthew J. McArthur, Michael W. Becker, Scott W. Ballinger, Satoshi Gojo, Roman A. Eliseev, Laura M. Calvi
Summary: Mitochondrial dysfunction is common in various conditions, and mitochondrial DNA (mtDNA) transfer may be a promising strategy for treatment. In this study, we successfully expanded mouse hematopoietic stem cells (HSCs) ex vivo and observed high engraftment of the donor cells in the host. We also found that HSCs from donor mice could transfer mtDNA to host cells, highlighting the utility of ex vivo expanded HSCs for mitochondrial transfer.
Article
Cell & Tissue Engineering
Daisuke Kami, Yosuke Suzuki, Masashi Yamanami, Takahiro Tsukimura, Tadayasu Togawa, Hitoshi Sakuraba, Satoshi Gojo
Summary: The study introduced a new ex vivo gene therapy platform using a transplant pack for cell transplantation to treat lysosomal diseases. The experimental findings demonstrated the survival and therapeutic enzyme production by transplanted cells in animal models, indicating the potential of this therapeutic strategy for lysosomal diseases.
CELL TRANSPLANTATION
(2021)
Article
Cardiac & Cardiovascular Systems
Tomoya Inoue, Keiichi Kanda, Masashi Yamanami, Daisuke Kami, Satoshi Gojo, Hitoshi Yaku
Summary: The study showed that short-duration ethanol dehydration did not compromise the mechanical properties of the pericardium while also improving surgical handling.
ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Cell & Tissue Engineering
Daisuke Kami, Masashi Yamanami, Takahiro Tsukimura, Hideki Maeda, Tadayasu Togawa, Hitoshi Sakuraba, Satoshi Gojo
CELL TRANSPLANTATION
(2020)