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Advanced Materials (Deerfield Beach,... Jun 2024Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in...
Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in human embryo research, makes investigating the mechanisms behind twinning practically infeasible. As a result, there is a significant knowledge gap regarding the origins and early phenotypic presentation of monochorionic twin embryos. In this study, a microthermoformed-based microwell screening platform is used to identify conditions that efficiently induce monochorionic twins in human stem cell-based blastocyst models, termed "twin blastoids". These twin blastoids contain a cystic GATA3+ trophectoderm-like epithelium encasing two distinct inner cell masses (ICMs). Morphological and morphokinetic analyses reveal that twinning occurs during the cavitation phase via splitting of the OCT4+ pluripotent core. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm-like region, ready for implantation. This is functionally tested in a microfluidic chip-based implantation assay with epithelial endometrium cells. Under defined flow regimes, twin blastoids show increased adhesion capacity compared to singleton blastoids, suggestive of increased implantation potential. In conclusion, the development of technology enabling large-scale formation of twin blastoids, coupled with high-sensitivity readout capabilities, presents an unprecedented opportunity for systematically exploring monochorionic twin formation and its impact on embryonic development.
Topics: Humans; Female; Pregnancy; Twinning, Monozygotic; Blastocyst; Embryo, Mammalian; Chorion; Bioengineering; Models, Biological; Embryo Implantation
PubMed: 38593372
DOI: 10.1002/adma.202313306 -
Science Immunology Apr 2024Although human twin studies have revealed the combined contribution of heritable and environmental factors in shaping immune system variability in blood, the...
Although human twin studies have revealed the combined contribution of heritable and environmental factors in shaping immune system variability in blood, the contribution of these factors to immune system variability in tissues remains unexplored. The human uterus undergoes constant regeneration and is exposed to distinct environmental factors. To assess uterine immune system variation, we performed a system-level analysis of endometrial and peripheral blood immune cells in monozygotic twins. Although most immune cell phenotypes in peripheral blood showed high genetic heritability, more variation was found in endometrial immune cells, indicating a stronger influence by environmental factors. Cytomegalovirus infection was identified to influence peripheral blood immune cell variability but had limited effect on endometrial immune cells. Instead, hormonal contraception shaped the local endometrial milieu and immune cell composition with minor influence on the systemic immune system. These results highlight that the magnitude of human immune system variation and factors influencing it can be tissue specific.
Topics: Female; Humans; Twins, Dizygotic; Twins, Monozygotic; Endometrium; Uterus; Immune System
PubMed: 38579017
DOI: 10.1126/sciimmunol.adj7168 -
Journal of Clinical Immunology Apr 2024
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Hodgkin Disease; Immunotherapy; T-Lymphocytes; Twins, Monozygotic; Cation Transport Proteins
PubMed: 38578340
DOI: 10.1007/s10875-024-01690-0 -
EBioMedicine May 2024Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D...
BACKGROUND
Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.
METHODS
We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.
FINDINGS
We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2).
INTERPRETATION
The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications.
FUNDING
Funding acknowledgements for each cohort can be found in the Supplementary Note.
Topics: Humans; Diabetes Mellitus, Type 2; DNA Methylation; CpG Islands; Female; Male; Genome-Wide Association Study; Genetic Predisposition to Disease; Middle Aged; Epigenesis, Genetic; Otx Transcription Factors; Diabetes Complications; Gene Expression Profiling
PubMed: 38574408
DOI: 10.1016/j.ebiom.2024.105096 -
JAMA Psychiatry Jun 2024
Topics: Humans; Obsessive-Compulsive Disorder; Male; Female; Diseases in Twins; Adult; Twins, Monozygotic; Twins, Dizygotic; Genetic Predisposition to Disease
PubMed: 38568562
DOI: 10.1001/jamapsychiatry.2024.0299 -
Journal of Orthopaedic Surgery and... Apr 2024The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully...
INTRODUCTION
The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully understood. While repetitive physical exercise-related stress is usually assumed to be the main risk factor for the occurrence of OCD, genetic predisposition could have an underestimated influence on the development of the disease.
CASE REPORT
We report a case of monozygotic twins with almost identical stages of bilateral osteochondrosis dissecans of the knee joint. In both patients, initially, a unilateral lesion occurred; despite restricted physical exercise, in the further course of the disease a lesion also developed on the contralateral side. While the lesion found most recently demonstrated an ongoing healing process at a 6-month follow-up, the other three lesions showed a natural course of healing under conservative treatment with significant clinical as well as radiological improvements after one year and complete consolidation in magnetic resonance imaging (MRI) after 2 years.
CONCLUSION
There could be a genetic component to the development of OCD, although this has not yet been proven. Based on a two-year MRI follow-up, we were able to show the self-limiting characteristics of juvenile osteochondrosis dissecans.
Topics: Humans; Knee Joint; Magnetic Resonance Imaging; Osteochondritis Dissecans; Osteochondrosis; Radiography; Twins, Monozygotic
PubMed: 38561825
DOI: 10.1186/s13018-024-04683-2 -
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke... Mar 2024
Topics: Humans; Twins, Monozygotic; Head; Rhabdomyosarcoma; Neck; Head and Neck Neoplasms; Combined Modality Therapy
PubMed: 38561268
DOI: 10.3760/cma.j.cn115330-20230827-00063 -
Development and Psychopathology Apr 2024The present study examined the longitudinal associations between three dimensions of temperament - activity, affect-extraversion, and task orientation - and childhood...
The present study examined the longitudinal associations between three dimensions of temperament - activity, affect-extraversion, and task orientation - and childhood aggression. Using 131 monozygotic and 173 dizygotic (86 same-sex) twin pairs from the Louisville Twin Study, we elucidated the ages, from 6 to 36 months, at which each temperament dimension began to correlate with aggression at age 7. We employed latent growth modeling to show that developmental increases (i.e., slopes) in activity were positively associated with aggression, whereas increases in affect-extraversion and task orientation were negatively associated with aggression. Genetically informed models revealed that correlations between temperament and aggression were primarily explained by common genetic variance, with nonshared environmental variance accounting for a small proportion of each correlation by 36 months. Genetic variance explained the correlations of the slopes of activity and task orientation with aggression. Nonshared environmental variance accounted for almost half of the correlation between the slopes of affect-extraversion and aggression. Exploratory analyses revealed quantitative sex differences in each temperament-aggression association. By establishing which dimensions of temperament correlate with aggression, as well as when and how they do so, our work informs the development of future child and family interventions for children at highest risk of aggression.
PubMed: 38557599
DOI: 10.1017/S0954579424000634 -
Stem Cell Research Jun 2024Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems...
Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems from point mutations in mitochondrial DNA (mtDNA), with key mutations being m.3460G > A, m.11778G > A, and m.14484 T > C. Fibroblasts from identical twins, sharing m.14484 T > C and m.10680G > A variants each with 70 % heteroplasmy, were used to generate iPSC lines. Remarkably, one twin, a LHON patient, displayed symptoms, while the other, a carrier, remained asymptomatic. These iPSCs offer a valuable tool for studying factors influencing disease penetrance and unravelling the role of m.10680G > A, which is still debated.
Topics: Humans; Optic Atrophy, Hereditary, Leber; Induced Pluripotent Stem Cells; Twins, Monozygotic; DNA, Mitochondrial; Male; Mitochondria; Female; Point Mutation; Adult
PubMed: 38552355
DOI: 10.1016/j.scr.2024.103406 -
Journal of Surgical Case Reports Mar 2024Studies in monozygotic (MZ) twins may help researchers elucidate the complex relationships between genetic and environmental factors on weight loss. We present a world...
Studies in monozygotic (MZ) twins may help researchers elucidate the complex relationships between genetic and environmental factors on weight loss. We present a world first of MZ twins who have undergone the single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) procedure who have identical weights 3 years post-operatively. Two MZ twin 49-year-old females were assessed preoperatively and were indicated for the SADI-S procedure. They underwent surgery in 2020 by the same surgical team. Three years later post-operatively they had identical weights of 62 kg (and a BMI of 23) and %EWL of 126 and 124% respectively. SADI-S is a novel bariatric procedure for morbid obesity. Studies have found concordant epigenetic patterns in patients who have undergone bariatric surgery as well as MZ twins who have hypocaloric diets. Genetics exert a strong influence in weight management. Surgical management as well as a collaborative multidisciplinary approach is beneficial in supporting long lasting weight loss in bariatric surgery.
PubMed: 38549721
DOI: 10.1093/jscr/rjae192