HiPS-Endothelial Cells Acquire Cardiac Endothelial Phenotype in Co-culture With hiPS-Cardiomyocytes DOI Creative Commons
Emmi Helle, Minna Ampuja, Alexandra Dainis

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Aug. 6, 2021

Cell-cell interactions are crucial for organ development and function. In the heart, endothelial cells engage in bidirectional communication with cardiomyocytes regulating cardiac growth. We aimed to elucidate organotypic of cardiomyocyte cell crosstalk using human induced pluripotent stem (hiPSC). Single-cell RNA sequencing was performed hiPSC-derived (hiPS-CMs) (hiPS-ECs) mono- co-culture. The presence hiPS-CMs led increased expression transcripts related vascular maturation, development, as well endocardium-specific genes hiPS-ECs. Interestingly, co-culture myofibrillar MYL7 MYL4 protein detected Major regulators BMP- Notch-signaling pathways were both types These results reflect findings from animal studies extend them cells, demonstrating importance EC-CM during development.

Language: Английский

Genomic frontiers in congenital heart disease DOI
Sarah U. Morton, Daniel Quiat, Jonathan G. Seidman

et al.

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 19(1), P. 26 - 42

Published: July 16, 2021

Language: Английский

Citations

161
Spatially organized cellular communities form the developing human heart DOI Creative Commons
Elie N. Farah, Robert Hu, Colin Kern

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8005), P. 854 - 864

Published: March 13, 2024

Abstract The heart, which is the first organ to develop, highly dependent on its form function 1,2 . However, how diverse cardiac cell types spatially coordinate create complex morphological structures that are crucial for heart remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization resolve identity of develop human heart. This approach also provided a spatial mapping individual cells enables illumination their organization into cellular communities distinct structures. We discovered many these further specified subpopulations exclusive specific communities, support specialization according ecosystem and anatomical region. In particular, ventricular cardiomyocyte displayed an unexpected laminar across wall formed, other subpopulations, several communities. Interrogating cell–cell interactions within using vivo conditional genetic mouse models vitro pluripotent stem systems revealed multicellular signalling pathways orchestrate during morphogenesis. These detailed findings social constructing remodelling offer new insights structural diseases engineering tissues repair.

Language: Английский

Citations

71
Single-Cell Transcriptomics Identified Fibrosis-Activated Valve Interstitial Cells Involved in Functional Tricuspid Regurgitation DOI Creative Commons

Ruojin Zhao,

Mengxia Fu, Songren Shu

et al.

JACC Asia, Journal Year: 2025, Volume and Issue: 5(3), P. 478 - 495

Published: March 1, 2025

The treatment of functional tricuspid regurgitation (TR) is still controversial. Characterizing the cellular composition valve and identifying molecular alterations each cell type in valves with TR will advance our understanding mechanisms guide improvements treatment. authors aimed to investigate changes gene expression patterns cells regurgitant shed light on TR. To improve pathogenesis TR, we performed single-cell RNA sequencing from 10 patients, including 5 patients moderate-to-severe nondiseased control subjects. Multiplexed fluorescence was used detect spatial distributions valvular states validated cell-cell interaction. We assessed transcriptional profiles 84,102 identified 6 major clusters, along 25 subtypes, specimens. Valve interstitial (VICs) were largest population. VICs lymphoid exhibited more heterogeneity patients. higher activity toward matrifibrocyte-like myofibroblast-like differentiation, myeloid activated immune response, promoted fibrosis. In alternation COMP-CD47 FGF2-FGFR1 interaction may occur specimens, which serve as promising therapeutic targets for Our atlas highlights transcriptomic underlying functions interactions human defines perturbations VIC clusters fibrosis activation accumulated valves.

Language: Английский

Citations

3
Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease DOI Creative Commons
Irfan S. Kathiriya, Kavitha S. Rao, Giovanni Iacono

et al.

Developmental Cell, Journal Year: 2020, Volume and Issue: 56(3), P. 292 - 309.e9

Published: Dec. 15, 2020

Language: Английский

Citations

87
Lifespan Perspective on Congenital Heart Disease Research DOI
Gerhard‐Paul Diller, Alexandra Arvanitaki, Alexander R. Opotowsky

et al.

Journal of the American College of Cardiology, Journal Year: 2021, Volume and Issue: 77(17), P. 2219 - 2235

Published: April 27, 2021

Language: Английский

Citations

80
Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease DOI Creative Commons

Mohamed Ameen,

Laksshman Sundaram, Mengcheng Shen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(26), P. 4937 - 4953.e23

Published: Dec. 1, 2022

Language: Английский

Citations

63
Genetics of congenital heart disease: a narrative review of recent advances and clinical implications DOI Open Access
Jun Yasuhara, Vidu Garg

Translational Pediatrics, Journal Year: 2021, Volume and Issue: 10(9), P. 2366 - 2386

Published: Aug. 30, 2021

Congenital heart disease (CHD) is the most common human birth defect and remains a leading cause of mortality in childhood. Although advances clinical management have improved survival children with CHD, adult survivors commonly experience cardiac non-cardiac comorbidities, which affect quality life prognosis. Therefore, elucidation genetic etiologies CHD not only has important implications for counseling patients families but may also impact outcomes by identifying at-risk patients. Recent advancements technologies, including massively parallel sequencing, allowed discovery new CHD. variant prioritization interpretation pathogenicity remain challenges field genomics, single-cell genomics functional using cellular animal models potential to provide novel insights into underlying mechanisms its associated morbidities. In this review, we an updated summary established contributors discuss recent our understanding architecture along current variation. Furthermore, highlight findings predict potentially improve

Language: Английский

Citations

59
Computational profiling of hiPSC-derived heart organoids reveals chamber defects associated with NKX2-5 deficiency DOI Creative Commons
Wei Feng, Hannah Schriever, Shan Jiang

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: April 29, 2022

Abstract Heart organoids have the potential to generate primary heart-like anatomical structures and hold great promise as in vitro models for cardiac disease. However, their properties not yet been fully studied, which hinders wide spread application. Here we report development of differentiation systems ventricular atrial heart organoids, enabling study diseases with chamber defects. We show that our chamber-specific comprising major cell types, use single RNA sequencing together sample multiplexing characterize cells generate. To end, developed a machine learning label transfer approach leveraging type, chamber, laterality annotations available human fetal cells. then used this model analyze organoid from an isogeneic line carrying Ebstein’s anomaly associated genetic variant NKX2-5 , successfully recapitulated disease’s atrialized In summary, established workflow integrating computational analysis normal disease states.

Language: Английский

Citations

46
Uncompensated mitochondrial oxidative stress underlies heart failure in an iPSC-derived model of congenital heart disease DOI Creative Commons
Xinxiu Xu, Kang Jin, Abha Bais

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(5), P. 840 - 855.e7

Published: April 7, 2022

Language: Английский

Citations

43
Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring DOI Creative Commons

Riitta Turunen,

Anna Pulakka, Johanna Metsälä

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(1), P. e2350579 - e2350579

Published: Jan. 5, 2024

Importance Maternal diabetes and overweight or obesity are known to be associated with increased risk of congenital heart defects (CHDs) in offspring, but there no large studies analyzing outcomes these factors 1 model. Objective To investigate the association maternal CHDs among offspring Design, Setting, Participants This nationwide, population-based register study was conducted a birth cohort from Finland consisting all children born between 2006 2016 (620 751 individuals) their mothers. Data were analyzed January 2022 until November 2023. Exposures prepregnancy body mass index (BMI; calculated as weight kilograms divided by height meters squared), categorized underweight (<18.5), normal (18.5-24.9), (25.0-29.9), (≥30), assessed. status, classified diabetes, type (T1D), 2 other gestational Main Outcomes Measures Odds ratios (ORs) isolated found. In addition, 9 anatomical CHD subgroups studied. Results Of 620 (316 802 males [51.0%]; 573 259 mothers aged 20-40 years [92.3%]) during period, 10 254 (1.7%) had an CHD. T1D odds having child any (OR, 3.77 [95% CI, 3.26-4.36]) 6 (OR range, 3.28 1.55-6.95] for septal 7.39 3.00-18.21] transposition great arteries) compared diabetes. left ventricular outflow tract obstruction 1.28 1.10-1.49]) 0.92 0.86-0.98]), complex 2.70 1.14-6.43]) right 1.31 1.09-1.58]) BMI. Conclusions Relevance found that most types while decreased defects. These different profiles may suggest distinct underlying teratogenic mechanisms.

Language: Английский

Citations

17