Institution
Kettering University
Education•Flint, Michigan, United States•
About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.
Topics: RNA, Antigen, DNA, Cancer, Population
Papers published on a yearly basis
Papers
More filters
••
TL;DR: The derivation of patient-specific FD-iPSCs and the directed differentiation into cells of all three germ layers including peripheral neurons are reported, illustrating the promise of iPSC technology for gaining new insights into human disease pathogenesis and treatment.
Abstract: The isolation of human induced pluripotent stem cells (iPSCs) offers a new strategy for modelling human disease. Recent studies have reported the derivation and differentiation of disease-specific human iPSCs. However, a key challenge in the field is the demonstration of disease-related phenotypes and the ability to model pathogenesis and treatment of disease in iPSCs. Familial dysautonomia (FD) is a rare but fatal peripheral neuropathy, caused by a point mutation in the IKBKAP gene involved in transcriptional elongation. The disease is characterized by the depletion of autonomic and sensory neurons. The specificity to the peripheral nervous system and the mechanism of neuron loss in FD are poorly understood owing to the lack of an appropriate model system. Here we report the derivation of patient-specific FD-iPSCs and the directed differentiation into cells of all three germ layers including peripheral neurons. Gene expression analysis in purified FD-iPSC-derived lineages demonstrates tissue-specific mis-splicing of IKBKAP in vitro. Patient-specific neural crest precursors express particularly low levels of normal IKBKAP transcript, suggesting a mechanism for disease specificity. FD pathogenesis is further characterized by transcriptome analysis and cell-based assays revealing marked defects in neurogenic differentiation and migration behaviour. Furthermore, we use FD-iPSCs for validating the potency of candidate drugs in reversing aberrant splicing and ameliorating neuronal differentiation and migration. Our study illustrates the promise of iPSC technology for gaining new insights into human disease pathogenesis and treatment.
892 citations
••
TL;DR: Analysis of CFU-F proliferative status by the thymidine suicide technique indicated that this cell was noncycling in individuals with undisturbed bone marrow function and data support the conclusion that the colonies described in this study are of fibroblastic nature.
882 citations
••
TL;DR: Secretion of infectious Abelson leukemia virus by two of the cloned cell lines provides conclusive evidence that the Abelson virus is capable of productively infecting the macrophage cell type.
866 citations
••
TL;DR: These findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint-blockade-induced immune responses are driven by distinct cellular mechanisms, and that checkpoint blockade targets only specific subsets of tumor-infiltrating T cell populations.
856 citations
••
849 citations
Authors
Showing all 6853 results
Name | H-index | Papers | Citations |
---|---|---|---|
Joan Massagué | 189 | 408 | 149951 |
Chris Sander | 178 | 713 | 233287 |
Timothy A. Springer | 167 | 669 | 122421 |
Murray F. Brennan | 161 | 925 | 97087 |
Charles M. Rice | 154 | 561 | 83812 |
Lloyd J. Old | 152 | 775 | 101377 |
Howard I. Scher | 151 | 944 | 101737 |
Paul Tempst | 148 | 309 | 89225 |
Pier Paolo Pandolfi | 146 | 529 | 88334 |
Barton F. Haynes | 144 | 911 | 79014 |
Jedd D. Wolchok | 140 | 713 | 123336 |
James P. Allison | 137 | 483 | 83336 |
Harold E. Varmus | 137 | 496 | 76320 |
Scott W. Lowe | 134 | 396 | 89376 |
David S. Klimstra | 133 | 564 | 61682 |