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
Jianyi Ding, Yongqin Li, Andre Larochelle
Summary: The ability to produce human hematopoietic stem cells (HSCs) in the laboratory holds great potential for cellular therapy of blood diseases. However, current differentiation protocols for generating HSCs from pluripotent stem cells (PSCs) lack clinical relevance and result in limited engraftment and differentiation capabilities. This review discusses how intrinsic cues and extrinsic environmental inputs have been integrated into PSC differentiation protocols to enhance the emergence of definitive hematopoiesis, and explores the role of genomics in advancing this field.
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.
Article
Cell & Tissue Engineering
Ana Belen Alvarez-Palomo, Jordi Requena-Osete, Raul Delgado-Morales, Victoria Moreno-Manzano, Carme Grau-Bove, Agueda M. Tejera, Manel Juan Otero, Carme Barrot, Irene Santos-Barriopedro, Alejandro Vaquero, Jovita Mezquita-Pla, Sebastian Moran, Carlos Hobeich Naya, Iris Garcia-Martinez, Francisco Vidal Perez, Maria A. Blasco, Manel Esteller, Michael J. Edel
Summary: The study demonstrates that utilizing synthetic mRNA transfection of CYCLIN D1 during reprogramming repairs DNA and significantly improves the genetic stability of human iPSC. This method reduces various genetic instabilities, decreases DNA damage, promotes correct protein expression, and reduces single-nucleotide polymorphism changes per chromosome.
Article
Cell Biology
Alexandra Neaverson, Malin H. L. Andersson, Osama A. Arshad, Luke Foulser, Mary Goodwin-Trotman, Adam Hunter, Ben Newman, Minal Patel, Charlotte Roth, Tristan Thwaites, Helena Kilpinen, Matthew E. Hurles, Andrew Day, Sebastian S. Gerety
Summary: Efficient and effective methods for converting human induced pluripotent stem cells into differentiated derivatives are critical for performing robust, large-scale studies of development and disease modelling, and for providing a source of cells for regenerative medicine. Here, we describe a 14-day neural differentiation protocol which allows for the scalable, simultaneous differentiation of multiple iPSC lines into cortical neural stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Engineering, Biomedical
Xingchi Chen, Chang Liu, Matthew Wadsworth, Eric Z. Zeng, Tristan Driscoll, Changchun Zeng, Yan Li
Summary: This study investigates the differentiation capacity of human induced pluripotent stem cells on different auxetic polyurethane foams with different characteristics, and finds that the properties of the foams affect cell adhesion density and differentiation capacity.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Endocrinology & Metabolism
Ila Tewari Jasra, Nerea Cuesta-Gomez, Kevin Verhoeff, Braulio A. Marfil-Garza, Nidheesh Dadheech, A. M. James Shapiro
Summary: This review summarizes the roles and mechanisms of mitochondria in somatic cell reprogramming to iPSCs and the metabolic shift associated with directed differentiation into pancreatic beta-like cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemical Research Methods
Julia Vallverdu, Raquel A. Martinez Garcia de la Torre, Inge Mannaerts, Stefaan Verhulst, Ayla Smout, Mar Coll, Silvia Arino, Teresa Rubio-Tomas, Beatriz Aguilar-Bravo, Celia Martinez-Sanchez, Delia Blaya, Catherine M. Verfaillie, Leo A. van Grunsven, Pau Sancho-Bru
Summary: Human iPSCs are differentiated into HSCs with growth factors for in vitro modeling. The protocol yields iPSC-HSCs with phenotypic and functional characteristics of primary HSCs, suitable for high-throughput in vitro studies. Coculturing iPSC-HSCs with hepatocytes allows for the formation of 3D hepatic spheroids, enabling modeling and drug screening studies.
Article
Multidisciplinary Sciences
Jingyang Guan, Guan Wang, Jinlin Wang, Zhengyuan Zhang, Yao Fu, Lin Cheng, Gaofan Meng, Yulin Lyu, Jialiang Zhu, Yanqin Li, Yanglu Wang, Shijia Liuyang, Bei Liu, Zirun Yang, Huanjing He, Xinxing Zhong, Qijing Chen, Xu Zhang, Shicheng Sun, Weifeng Lai, Yan Shi, Lulu Liu, Lipeng Wang, Cheng Li, Shichun Lu, Hongkui Deng
Summary: This study demonstrates the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells, which exhibit key features of embryonic stem cells. The induction of an intermediate plastic state and inhibition of the JNK pathway are crucial for successful chemical reprogramming.
Review
Biochemistry & Molecular Biology
Agnieszka Fus-Kujawa, Barbara Mendrek, Anna Trybus, Karolina Bajdak-Rusinek, Karolina L. Stepien, Aleksander L. Sieron
Summary: Induced pluripotent stem cells (iPSCs) show potential in gene therapy and disease modeling. To safely apply this technology in clinical settings, optimal reprogramming factors and vectors must be considered to reduce the risk of insertional tumorigenesis.
Article
Peripheral Vascular Disease
Lu Liu, Charlene Jouve, Josephine Henry, Takiy-Eddine Berrandou, Jean-Sebastien Hulot, Adrien Georges, Nabila Bouatia-Naji
Summary: This study characterized the cellular phenotypes, epigenomic and proteomic profiles of smooth muscle cells (SMCs) derived from induced pluripotent stem cells (iPSCs) and evaluated their potential as cellular models for complex diseases. The iPSC-derived SMCs demonstrated different functional properties and gene expression profiles. These cellular models have the potential to investigate the functional regulation of genetic risk loci in major arterial diseases.
Article
Engineering, Biomedical
Hong Cao, Qian Zhou, Chungeng Liu, Yecen Zhang, Minghui Xie, Weihua Qiao, Nianguo Dong
Summary: This study investigates the effect of substrate stiffness on the differentiation of human-induced pluripotent stem cells (h-iPSCs) into valve endothelial-like cells (h-iVECs). The results show that moderate substrate stiffness can enhance the differentiation efficiency of h-iVECs and is regulated by the WNT/Calcineurin signaling pathway. This study emphasizes the importance of using substrate stiffness to achieve a more specific and mature differentiation of h-iVECs.
ACTA BIOMATERIALIA
(2022)
Article
Biochemistry & Molecular Biology
Eleanor Luce, Clara Steichen, Soumeya Abed, Anne Weber, Philippe Leboulch, Leila Maouche-Chretien, Anne Dubart-Kupperschmitt
Summary: The study demonstrates that siPSCs can differentiate into liver cells and self-organize into 3D structures, facilitating research on liver development and the development of co-culture systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Michiko Yamane, Nanako Takaoka, Koya Obara, Kyoumi Shirai, Ryoichi Aki, Yuko Hamada, Nobuko Arakawa, Robert M. Hoffman, Yasuyuki Amoh
Summary: Hair-follicle-associated pluripotent (HAP) stem cells, located in hair follicles, can differentiate into multiple cell types, including neurons and cardiomyocytes. Studies have shown that HAP stem cells treated with neural-induction medium can differentiate into dopaminergic neurons, which may potentially help improve symptoms of Parkinson's disease in the future.
Article
Cell Biology
Peng Cui, Ping Zhang, Lin Yuan, Li Wang, Xin Guo, Guanghui Cui, Yanmin Zhang, Minghua Li, Xiaowei Zhang, Xiaoqiang Li, Yuxin Yin, Zhendong Yu
Summary: HIF-1α knockdown affects the pluripotency and self-renewal potential of hiPSCs, promoting NSC differentiation and development potential possibly through the MFN2-mediated Wnt/beta-catenin signaling pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Dermatology
Rie Takahashi, Adrienne Grzenda, Thomas F. Allison, Jeffrey Rawnsley, Samuel J. Balin, Shan Sabri, Kathrin Plath, William E. Lowry
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Donald B. Kohn, Claire Booth, Elizabeth M. Kang, Sung-Yun Pai, Kit L. Shaw, Giorgia Santilli, Myriam Armant, Karen F. Buckland, Uimook Choi, Suk See De Ravin, Morna J. Dorsey, Caroline Y. Kuo, Diego Leon-Rico, Christine Rivat, Natalia Izotova, Kimberly Gilmour, Katie Snell, Jinhua Xu-Bayford Dip, Jinan Darwish, Emma C. Morris, Dayna Terrazas, Leo D. Wang, Christopher A. Bauser, Tobias Paprotka, Douglas B. Kuhns, John Gregg, Hayley E. Raymond, John K. Everett, Geraldine Honnet, Luca Biasco, Peter E. Newburger, Frederic D. Bushman, Manuel Grez, H. Bobby Gaspar, David A. Williams, Harry L. Malech, Anne Galy, Adrian J. Thrasher, Karen F. Buckland, Christopher A. Bauser, Geraldine Honnet, Manuel Grez, H. Bobby Gaspar, Anne Galy, Adrian J. Thrasher
Article
Cell & Tissue Engineering
Haibin Xi, Justin Langerman, Shan Sabri, Peggie Chien, Courtney S. Young, Shahab Younesi, Michael Hicks, Karen Gonzalez, Wakana Fujiwara, Julia Marzi, Simone Liebscher, Melissa Spencer, Ben Van Handel, Denis Evseenko, Katja Schenke-Layland, Kathrin Plath, April D. Pyle
Article
Multidisciplinary Sciences
Amy Pandya-Jones, Yolanda Markaki, Jacques Serizay, Tsotne Chitiashvili, Walter R. Mancia Leon, Andrey Damianov, Constantinos Chronis, Bernadett Papp, Chun-Kan Chen, Robin McKee, Xiao-Jun Wang, Anthony Chau, Shan Sabri, Heinrich Leonhardt, Sika Zheng, Mitchell Guttman, Douglas L. Black, Kathrin Plath
Article
Cell & Tissue Engineering
Jingtao Guo, Enrique Sosa, Tsotne Chitiashvili, Xichen Nie, Ernesto Javier Rojas, Elizabeth Oliver, Kathrin Plath, James M. Hotaling, Jan-Bernd Stukenborg, Amander T. Clark, Bradley R. Cairns
Summary: This study provides insights into the complex changes in cell identity during human testis development in prenatal life, from the establishment of testicular cords to the transitioning of male primordial germ cells into cells resembling f0 spermatogonia. The analysis of single-cell transcriptomes reveals the coordinated and temporal development of embryonic, fetal, and postnatal male germline and somatic niche.
Article
Biochemical Research Methods
Weixian Deng, Jihui Sha, Kathrin Plath, James A. Wohlschlegel
Summary: In bottom-up proteomics, achieving deep proteome coverage requires peptide-level fractionation to simplify the complex peptide mixture. CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Cell Biology
Tsotne Chitiashvili, Iris Dror, Rachel Kim, Fei-Man Hsu, Rohan Chaudhari, Erica Pandolfi, Di Chen, Simone Liebscher, Katja Schenke-Layland, Kathrin Plath, Amander Clark
NATURE CELL BIOLOGY
(2020)
Article
Genetics & Heredity
David H. Gray, Isaac Villegas, Joseph Long, Jasmine Santos, Alexandra Keir, Alison Abele, Caroline Y. Kuo, Donald B. Kohn
Summary: X-linked agammaglobulinemia (XLA) is a genetic disorder characterized by low immunoglobulin levels and increased infection risks. Gene editing in hematopoietic stem cells of XLA patients aims to correct the Bruton's tyrosine kinase (BTK) gene mutation and restore B cell development. The CRISPR-Cas9 platform enables precise integration of corrective BTK cDNA, potentially offering therapeutic levels of gene therapy for XLA.
Article
Immunology
Carolyn H. Baloh, Samiksha A. Borkar, Kai-Fen Chang, Jiqiang Yao, Michael S. Hershfield, Suhag H. Parikh, Donald B. Kohn, Maureen M. Goodenow, John W. Sleasman, Li Yin
Summary: Based on deep sequencing, gene therapy resulted in an IgHV repertoire with molecular diversity similar to healthy infants.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Cell Biology
Weixian Deng, Elsie C. Jacobson, Amanda J. Collier, Kathrin Plath
Summary: The understanding of iPSC reprogramming has provided insights into the mechanisms that safeguard somatic cell identity, drive epigenetic reprogramming, and underlie cell fate specification in vivo. The combinatorial action of TFs has emerged as the key mechanism for the direct and indirect effects of reprogramming factors that induce the remodelling of the enhancer landscape. The interplay of TFs in iPSC reprogramming also yields trophectoderm-and extraembryonic endoderm-like cell populations, uncovering an intriguing plasticity of cell states and opening new avenues for exploring cell fate decisions during early embryogenesis.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2021)
Article
Oncology
Jiaying Han, Kevin Tam, Curtis Tam, Roger P. Hollis, Donald B. Kohn
Summary: Lentiviral vectors are efficient tools for gene therapy, but their production can be hindered by limitations such as low titers and reduced gene transfer capacity. This study identified host restriction factors in packaging cells and developed a CRISPRed HEK293T cell line to disrupt these factors, leading to significant increases in viral titers. Overexpression of transcription elongation factors SPT4 and SPT5 during packaging also improved LV production. These approaches have the potential to benefit various gene therapy applications.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Hematology
Shanna L. White, Thomas D. Lee, Traci Toy, Judith E. Carroll, Lilian Polsky, Beatriz Campo Fernandez, Alejandra Davila, Donald B. Kohn, Vivian Y. Chang
Summary: The study investigated the impact of autologous stem cell transplant with gene therapy on telomere lengths (TL) and clonal hematopoiesis of indeterminate potential (CHIP) in pediatric patients with adenosine deaminase-deficient severe combined immune deficiency. The findings suggest the need for further research to reveal the underlying genetic risk of malignancy in participants undergoing gene therapy.
Review
Developmental Biology
William B. Tu, Heather R. Christofk, Kathrin Plath
Summary: Diet plays a crucial role in maintaining health throughout life, influencing cell fate decisions, maintaining tissue homeostasis, and mitigating the effects of aging. This review highlights the impact of common diets and specific nutrients on cell fate decisions in both healthy and disease contexts, as well as the potential of new models, technologies, and resources to advance dietary approaches for promoting healthy development and improving disease treatments.
Review
Immunology
Donald B. Kohn
Summary: ADA SCID is a severe inborn immune deficiency disease that can be effectively treated using gene therapy. Continuous improvements in treatment methods have led to significant immune restoration and stable engraftment of gene-corrected hematopoietic stem cells in most ADA SCID patients. However, achieving sustained availability and access to this therapy remains challenging.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Cell Biology
Jerry Hung-Hao Lo, Miguel Edwards, Justin Langerman, Rupa Sridharan, Kathrin Plath, Stephen T. Smale
Summary: By examining dynamic ranges of gene expression, the authors found that Oct4 and Sox2 binding is enriched near genes with large dynamic ranges of expression. Their results suggest that Oct4 and Sox2 directly establish both active and silent transcriptional states in pluripotent cells at a large number of genes subject to dynamic regulation.
GENES & DEVELOPMENT
(2022)