scholarly journals PAX1 is essential for development and function of the human thymus

2020 ◽  
Vol 5 (44) ◽  
pp. eaax1036 ◽  
Author(s):  
Yasuhiro Yamazaki ◽  
Raul Urrutia ◽  
Luis M. Franco ◽  
Silvia Giliani ◽  
Kejian Zhang ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Rare Variants ◽  
Severe Combined Immunodeficiency ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
Thymus Development ◽  
Induced Pluripotent ◽  
And Function ◽  
Epithelial Progenitor Cells

We investigated the molecular and cellular basis of severe combined immunodeficiency (SCID) in six patients with otofaciocervical syndrome type 2 who failed to attain T cell reconstitution after allogeneic hematopoietic stem cell transplantation, despite successful engraftment in three of them. We identified rare biallelic PAX1 rare variants in all patients. We demonstrated that these mutant PAX1 proteins have an altered conformation and flexibility of the paired box domain and reduced transcriptional activity. We generated patient-derived induced pluripotent stem cells and differentiated them into thymic epithelial progenitor cells and found that they have an altered transcriptional profile, including for genes involved in the development of the thymus and other tissues derived from pharyngeal pouches. These results identify biallelic, loss-of-function PAX1 mutations as the cause of a syndromic form of SCID due to altered thymus development.

scholarly journals Diabetic Endothelial Cells Differentiated From Patient iPSCs Show Dysregulated Glycine Homeostasis and Senescence Associated Phenotypes

2021 ◽  
Vol 9 ◽  
Author(s):  
Liping Su ◽  
Xiaocen Kong ◽  
Sze Jie Loo ◽  
Yu Gao ◽  
Jean-Paul Kovalik ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Transfer ◽  
Angiogenic Potential ◽  
Patients With Diabetes ◽  
Induced Pluripotent

Induced pluripotent stem cells derived cells (iPSCs) not only can be used for personalized cell transfer therapy, but also can be used for modeling diseases for drug screening and discovery in vitro. Although prior studies have characterized the function of rodent iPSCs derived endothelial cells (ECs) in diabetes or metabolic syndrome, feature phenotypes are largely unknown in hiPSC-ECs from patients with diabetes. Here, we used hiPSC lines from patients with type 2 diabetes mellitus (T2DM) and differentiated them into ECs (dia-hiPSC-ECs). We found that dia-hiPSC-ECs had disrupted glycine homeostasis, increased senescence, and impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. These signature phenotypes will be helpful to establish dia-hiPSC-ECs as models of endothelial dysfunction for understanding molecular mechanisms of disease and for identifying and testing new targets for the treatment of endothelial dysfunction in diabetes.

scholarly journals From patient-specific induced pluripotent stem cells to clinical translation in long QT syndrome Type 2

2019 ◽  
Vol 40 (23) ◽  
pp. 1832-1836 ◽  
Author(s):  
Peter J Schwartz ◽  
Massimiliano Gnecchi ◽  
Federica Dagradi ◽  
Silvia Castelletti ◽  
Gianfranco Parati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Long Qt Syndrome ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Syndrome Type ◽  
Long Qt ◽  
Qt Syndrome ◽  
Induced Pluripotent

scholarly journals Inhalational delivery of induced pluripotent stem cell secretome improves postpneumonectomy lung structure and function

2020 ◽  
Vol 129 (5) ◽  
pp. 1051-1061
Author(s):  
D. Merrill Dane ◽  
Khoa Cao ◽  
Yu-An Zhang ◽  
Kemp H. Kernstine ◽  
Amiq Gazdhar ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Induced Pluripotent Stem Cell ◽  
Repeated Administration ◽  
Control Treatment ◽  
Surgical Removal ◽  
Adaptive Responses ◽  
Lung Structure ◽  
Secretory Products ◽  
Induced Pluripotent ◽  
And Function

To examine whether the secreted products of human induced pluripotent stem cells (iPSCs) facilitate innate adaptive responses following loss of lung tissue, adult dogs underwent surgical removal of one lung, then received repeated administration of iPSC secretory products via inhalational delivery compared with control treatment. Inhalation of iPSC secretory products enhanced capillary formation and beneficial structural remodeling in the remaining lung, leading to improved lung function.

Sign in / Sign up

Export Citation Format

Share Document