Article
Cell & Tissue Engineering
Carlos Carrascoso-Rubio, Hidde A. Zittersteijn, Laura Pintado-Berninches, Beatriz Fernandez-Varas, M. Luz Lozano, Cristina Manguan-Garcia, Leandro Sastre, Juan A. Bueren, Rosario Perona, Guillermo Guenechea
Summary: Dyskeratosis congenita (DC) is a rare genetic disorder causing bone marrow failure. Current curative treatment involves allogeneic hematopoietic stem cell transplantation. This study successfully generated DC-like human hematopoietic stem cells to investigate innovative therapies and understand the molecular basis of the disease.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Multidisciplinary Sciences
Ho-Chang Jeong, Siddharth Shukla, Wilson Chun Fok, Thao Ngoc Huynh, Luis Francisco Zirnberger Batista, Roy Parker
Summary: Mutations in the USB1 gene result in hematopoietic failure in patients with poikiloderma with neutropenia. The exact mechanism behind this condition has not been determined, as pre-mRNA splicing remains unaffected. In this study, human embryonic stem cells with the PN-associated mutation in USB1 were generated, and it was found that dysregulated microRNA levels contribute to the hematopoietic failure. Inhibition of PAPD5/7, enzymes responsible for adding 3'-end adenylated tails, rescued hematopoiesis in USB1 mutants, suggesting it as a potential therapy for PN.
Letter
Medicine, Research & Experimental
Saeed Dorgaleleh, Karim Naghipoor, Amir Hozhabrpour, Hassan Vahidnezhad
Summary: Dyskeratosis Congenita (DC) is a rare and heterogeneous disease with shorter telomere length. Studies have shown that individuals with a short telomere background are more likely to experience severe symptoms and higher mortality rate related to COVID-19. This study hypothesized that patients with DC are at a higher risk of developing symptomatic COVID-19 requiring further clinical care.
MEDICAL HYPOTHESES
(2022)
Article
Biology
Rafael Jesus Fernandez, Zachary J. G. Gardner, Katherine J. Slovik, Derek C. Liberti, Katrina N. Estep, Wenli Yang, Qijun Chen, Garrett T. Santini, Javier Perez, Sarah Root, Ranvir Bhatia, John W. Tobias, Apoorva Babu, Michael P. Morley, David B. Frank, Edward E. Morrisey, Christopher J. Lengner, F. Brad Johnson
Summary: DC is a rare genetic disorder that causes short telomeres and early onset of age-related diseases. Using iAT2 cells to model, it is shown that shortened telomeres lead to cell senescence and Wnt signaling defects. The study suggests that Wnt agonists may be potential therapies for DC-related pathologies.
Article
Genetics & Heredity
Michele Callea, Diego Martinelli, Francisco Cammarata-Scalisi, Chiara Grimaldi, Houweyda Jilani, Piercesare Grimaldi, Colin Eric Willoughby, Antonino Morabito
Summary: Dyskeratosis congenita is a genetic syndrome with diverse clinical manifestations, including bone marrow failure and tumors. This review discusses the clinical characteristics, molecular genetics, disease progression, treatment options, and differential diagnosis of the disease, providing personalized medical assessment and family genetic counseling.
Review
Biochemistry & Molecular Biology
Nozomu Kawashima, Valentino Bezzerri, Seth J. Corey
Summary: Hereditary bone marrow failure syndromes (IBMFSs) are a group of rare genetic disorders, including Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia, and others. Mutations in specific genes involved in DNA damage response, ribosome structure or assembly, or telomere maintenance are responsible for the development of these syndromes. This review discusses the pathogenetic mechanisms of IBMFSs and proposes a potential role for pro-inflammatory cytokines in mediating cytopenias and the transformation to myeloid neoplasia. Anti-inflammatory therapies may hold promise in the treatment of these disorders.
Article
Behavioral Sciences
Ming-Jie Zhang, Ya-Xian Cao, Hui-Ying Wu, He-Hong Li
Summary: Hoyeraal-Hreidarsson syndrome is a severe variant of dyskeratosis congenita, with clinical features such as delayed development, skin pigmentation, nail/toenail dystrophy, thrombocytopenia, and anemia. CNS imaging findings show cerebellar hypoplasia, delayed myelination, hydrocephalus, brain atrophy, and calcification. Gene mutations in DKC1 and TINF2 can lead to the phenotypes of Hoyeraal-Hreidarsson syndrome, making cerebellar hypoplasia a key diagnostic feature.
BRAIN AND BEHAVIOR
(2021)
Article
Hematology
Samantha Nichele, Carmem Bonfim, G. D. Luiz Jr, Gisele Loth, Cilmara Kuwahara, Joanna Trennephol, Vaneuza A. M. Funke, Daniela E. Marinho, Adriana Koliski, Adriana M. Rodrigues, Rebeca T. G. Mousquer, Anders Fasth, Alberto C. M. Lima, Rodrigo T. Calado, Ricardo Pasquini
Summary: This retrospective study describes the outcomes of hematopoietic cell transplantation in patients with telomere biology diseases (TBD) between 1993 and 2019. The study found that although transplantation is a curative treatment option, non-hematological phenotypes remain a major challenge and are associated with poor long-term follow-up outcomes.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sophie Sleiman, Aren E. Marshall, Xiaomin Dong, Aziz Mhanni, Ismael Alidou-D'Anjou, Patrick Frosk, Samantha E. Marin, Zornitza Stark, Marc R. Del Bigio, Arran McBride, Simon Sadedin, Lyndon Gallacher, John Christodoulou, Kym M. Boycott, Francois Dragon, Kristin D. Kernohan
Summary: SHQ1 has been identified as associated with neurological diseases, including early-onset dystonia, and this study begins to uncover the molecular etiology of this novel condition.
HUMAN MOLECULAR GENETICS
(2022)
Article
Hematology
Neelam Giri, Blanche P. Alter, Sharon A. Savage, Pamela Stratton
Summary: Research shows that women with dyskeratosis congenita (DC) and related telomere biology disorders (TBD) may experience adverse impacts on reproductive health, leading to frequent gynaecological problems and pregnancy complications. Women with TBDs would benefit from multidisciplinary, coordinated care by haematology, gynaecology, and maternal-fetal medicine specialists.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jian Qin, Alexandre Garus, Chantal Autexier
Summary: This study reveals that mutations in the C-terminal extension (CTE) of dyskerin impair its interaction with hTR, leading to X-linked dyskeratosis congenita (X-DC) and related telomere syndromes. These mutations result in reduced binding to SHQ1 and defective binding to hTR. Furthermore, deletion of the CTE further reduces binding to hTR and disrupts the localization and interaction of dyskerin with other molecules.
HUMAN MOLECULAR GENETICS
(2023)
Article
Pediatrics
Liqing Wang, Jianwei Li, Qiuhong Xiong, Yong-An Zhou, Ping Li, Changxin Wu
Summary: This study reports the first discovery of a DKC1 gene mutation in a Chinese family, which is associated with the phenotype of mucocutaneous triad. The findings broaden the understanding of disease variation, genotype-phenotype correlations, and facilitate clinical diagnosis of DC in China.
FRONTIERS IN PEDIATRICS
(2022)
Article
Dermatology
Chunyu Yuan, Dongmei Deng, Jianqiu Yang, Simeng Liu, Qihong Qian, Min Chen, Shengru Zhou, Yujiang Li, Min Li
Summary: The study identified novel and missense mutations in the DKC1 gene in three Chinese families with X-linked DC. These mutations locally changed the structure of dyskerin and were predicted to have deleterious and natural effects on its function, respectively. These findings improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.
CLINICAL COSMETIC AND INVESTIGATIONAL DERMATOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Oguzhan Begik, Morghan C. Lucas, Leszek P. Pryszcz, Jose Miguel Ramirez, Rebeca Medina, Ivan Milenkovic, Sonia Cruciani, Huanle Liu, Helaine Graziele Santos Vieira, Aldema Sas-Chen, John S. Mattick, Schraga Schwartz, Eva Maria Novoa
Summary: This study demonstrated the potential of nanopore RNA sequencing for detecting and identifying various RNA modifications, including pseudouridine and 2'-O-methylation. By focusing on pseudouridine modification sites, the researchers revealed the distribution and dynamics of these modifications in cellular RNAs. The development of a software tool to estimate modification stoichiometries at each site provides a valuable tool for further research on RNA modifications.
NATURE BIOTECHNOLOGY
(2021)
Review
Oncology
Senthil Velan Bhoopalan, Marcin Wlodarski, Ulrike Reiss, Brandon Triplett, Akshay Sharma
Summary: Bone marrow failure in dyskeratosis congenita (DKC) is progressive, with allogeneic hematopoietic cell transplantation (HCT) being the only curative treatment. A reduced-intensity conditioning (RIC) regimen using fludarabine has shown to be feasible and safe for DKC patients undergoing HCT, without accelerating pulmonary damage in the short-to-medium term.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Biotechnology & Applied Microbiology
David Porubsky, Peter Ebert, Peter A. Audano, Mitchell R. Vollger, William T. Harvey, Pierre Marijon, Jana Ebler, Katherine M. Munson, Melanie Sorensen, Arvis Sulovari, Marina Haukness, Maryam Ghareghani, Peter M. Lansdorp, Benedict Paten, Scott E. Devine, Ashley D. Sanders, Charles Lee, Mark J. P. Chaisson, Jan O. Korbel, Evan E. Eichler, Tobias Marschall
Summary: This study introduces a reference-free workflow for diploid de novo genome assembly, combining single-cell strand sequencing with continuous long-read or high-fidelity sequencing data. By employing this strategy, the researchers successfully generated completely phased de novo genome assemblies for each haplotype of an individual of Puerto Rican descent, demonstrating high accuracy and contiguity with low switch error rates. A comparison of Oxford Nanopore Technologies and Pacific Biosciences phased assemblies identified regions that are preferential sites of contig breaks, regardless of sequencing technology or phasing algorithms.
NATURE BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Vincent C. T. Hanlon, Carl-Adam Mattsson, Diana C. J. Spierings, Victor Guryev, Peter M. Lansdorp
Summary: InvertypeR is a novel method for genotyping inversions based on a Bayesian model, eliminating the need for manual inspection and significantly improving the accuracy of inversion detection. The study results demonstrate that InvertypeR can effectively reduce genotypic discordance and identify multiple inversions that were previously unreported.
Article
Hematology
Peter M. Lansdorp
Summary: This article summarizes the role of telomeres in human health and disease and discusses the antagonistic role of telomere loss in aging and cancer. It proposes the Telomere Erosion in Disposable Soma theory.
Article
Cell Biology
Peter M. Lansdorp
Summary: Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting Hayflick limit may have allowed lifespan to increase by suppressing early tumor development but compromising cellular responses later in life. Average telomere length in leukocytes varies considerably between individuals, with females having longer telomeres than males. This difference in telomere length already exists at birth and corresponds to reported differences in average life expectancy between the sexes. The hypothesis that embryonic telomerase levels contribute to the sex differences in telomere length and lifespan requires further investigation.
Article
Virology
Francoise A. Gourronc, Michael R. Rebagliati, Breanna Kramer-Riesberg, Anthony M. Fleck, J. J. Patten, Kathleen Geohegan-Barek, Kelly N. Messingham, Robert A. Davey, Wendy Maury, Aloysius J. Klingelhutz
Summary: Adipocytes in adipose tissue may contribute to the inflammatory response and coagulopathy during EBOV pathogenesis.
Article
Biochemical Research Methods
Zeid Hamadeh, Vincent Hanlon, Peter M. Lansdorp
Summary: Mammalian genomes encode numerous helicases that play important roles in the repair of DNA lesions. Single-cell sequencing can be used to detect DNA repair events and infer the substrate specificity of helicases.
Review
Oncology
Peter Lansdorp
Summary: The number of telomere repeats varies greatly between chromosomes, cells, and species. Loss of telomere repeats limits cell proliferation and contributes to aging, but the mechanisms behind these processes are still not fully understood. Further research is needed to investigate the role of factors such as damaged telomeric DNA, replication errors, chromatin structure, and secondary DNA structures in telomere dynamics in different cell types.
FRONTIERS IN ONCOLOGY
(2022)
Review
Medicine, Research & Experimental
Peter M. Lansdorp
Summary: Telomeres and telomerase are crucial in human aging and cancer. The three drivers of human aging are the developmental program encoded in DNA, damage to the genome and epigenome, and the progressive loss of telomeric DNA. Malignant tumors arise when mutations and/or epimutations corrupt the developmental program and tumor suppression by telomere erosion.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Review
Genetics & Heredity
Vincent C. T. Hanlon, Peter M. Lansdorp, Victor Guryev
Summary: Polymorphic inversions are common in humans and have been linked to adaptation and disease. Various methods have been developed for the detection and genotyping of inversions, utilizing complex wet lab protocols or sophisticated bioinformatic analyses.
Editorial Material
Hematology
Kai J. Rogers, Meredith G. Parsons, Christopher S. Strouse, Umar Farooq, Annette J. Schlueter
TRANSFUSION AND APHERESIS SCIENCE
(2023)
Article
Multidisciplinary Sciences
Francoise A. Gourronc, Brynn K. Helm, Larry W. Robertson, Michael S. Chimenti, Hans-Joachim Lehmler, James A. Ankrum, Aloysius J. Klingelhutz
Summary: This study investigated the effects of PCB126 on gene transcription in human preadipocytes using RNAseq. The results showed that exposure to PCB126 caused changes in gene expression, which may be associated with the development of metabolic syndrome. These findings provide important insights into the impact of PCB126 and other dioxin-like compounds on health.
Article
Multidisciplinary Sciences
Timothy K. Turkalo, Antonio Maffia, Johannes J. Schabort, Samuel G. Regalado, Mital Bhakta, Marco Blanchette, Diana C. J. Spierings, Peter M. Lansdorp, Dirk Hockemeyer
Summary: Mutations of ATRX are common in cancers that undergo immortalization through the ALT pathway. The authors found that ALT features are repressed in ATRX-deficient embryonic stem cells, but induced by continuous telomere instability triggered during cell differentiation.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Kai J. Rogers, Sarah L. Mott, Meredith G. Parsons, Annette J. Schlueter
Summary: Accurately determining the processed blood volume required for collecting the targeted number of HSCs is crucial for optimizing PB HSC collections. Few studies have explored the utility of using different CEs in subpopulations of donors. Factors such as pre-procedure cell counts and relatedness to the recipient significantly impact CE.
JOURNAL OF CLINICAL APHERESIS
(2023)
Article
Multidisciplinary Sciences
Mariam Y. El-Hattab, Noah Sinclair, Jesse N. Liszewski, Michael V. Schrodt, Jacob Herrmann, Aloysius J. Klingelhutz, Edward A. Sander, James A. Ankrum
Summary: Adipocytes regulate tissues through the production of adipokines that act locally and systemically. They also play a critical role in regulating the healing process. In this study, a three-dimensional human adipocyte spheroid system was developed to understand how mature adipocytes signal to dermal fibroblasts to induce myofibroblast conversion. It was found that a factor secreted by mature adipocytes, identified as adiponectin, induces fibroblast to myofibroblast conversion through a pathway independent of TGF-beta 1.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2023)
Article
Biochemical Research Methods
Vincent C. T. Hanlon, Daniel D. Chan, Zeid Hamadeh, Yanni Wang, Carl-Adam Mattsson, Diana C. J. Spierings, Robin J. N. Coope, Peter M. Lansdorp
Summary: Single-cell Strand-seq technique generates directional genomic information for studying DNA repair, genome assembly, and mapping structural variation. In this study, a nanoliter-volume, one-pot (OP) Strand-seq library preparation protocol was developed, which allows cumulative addition of reagents, avoids DNA purification steps, and inactivates enzymes using a thermolabile protease. The OP-Strand-seq libraries can capture 10%-25% of the genome from a single-cell with reduced costs and increased throughput.
CELL REPORTS METHODS
(2022)