Institution
Boston Children's Hospital
Healthcare•Boston, Massachusetts, United States•
About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.
Topics: Population, Transplantation, Poison control, Intensive care, Health care
Papers published on a yearly basis
Papers
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TL;DR: It is shown that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled, and that hiPS cells acquire genetic modifications in addition to epigenetic modifications.
Abstract: Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.
1,198 citations
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Yale University1, University of Michigan2, University of California, Los Angeles3, Emory University4, Carnegie Mellon University5, Rutgers University6, Vanderbilt University7, Cornell University8, Baylor College of Medicine9, University of Illinois at Chicago10, Stanford University11, University of Pittsburgh12, University of Washington13, Princeton University14, Boston Children's Hospital15, Columbia University16, Howard Hughes Medical Institute17, Brown University18, Geisinger Health System19, Montreal Children's Hospital20
TL;DR: A genome-wide analysis of rare copy-number variation in 1124 autism spectrum disorder families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling, finds significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome.
1,198 citations
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TL;DR: Fas expression and function were analyzed in three children (including two siblings) with a lymphoproliferative syndrome, two of whom also had autoimmune disorders as discussed by the authors, showing that a large deletion in the gene encoding Fas and no detectable cell surface expression characterized the most affected patient.
Abstract: Fas (also known as Apo1 and CD95) is a cell surface receptor involved in apoptotic cell death. Fas expression and function were analyzed in three children (including two siblings) with a lymphoproliferative syndrome, two of whom also had autoimmune disorders. A large deletion in the gene encoding Fas and no detectable cell surface expression characterized the most affected patient. Clinical manifestations in the two related patients were less severe: Fas-mediated apoptosis was impaired and a deletion within the intracytoplasmic domain was detected. These findings illustrate the crucial regulatory role of Fas and may provide a molecular basis for some autoimmune diseases in humans.
1,193 citations
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TL;DR: The results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis, which may prove valuable as a diagnostic and prognostic tool to tailor therapies and assess responses to anticancer drugs.
Abstract: TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML). We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.
1,193 citations
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TL;DR: Fast-food consumption has strong positive associations with weight gain and insulin resistance, suggesting that fast food increases the risk of obesity and type 2 diabetes.
1,192 citations
Authors
Showing all 165661 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Frederick E. Shelton | 327 | 1485 | 295883 |
Robert Langer | 281 | 2324 | 326306 |
Graham A. Colditz | 261 | 1542 | 256034 |
Frank B. Hu | 250 | 1675 | 253464 |
George M. Whitesides | 240 | 1739 | 269833 |
Eugene Braunwald | 230 | 1711 | 264576 |
Ralph B. D'Agostino | 226 | 1287 | 229636 |
Mark J. Daly | 204 | 763 | 304452 |
Eric B. Rimm | 196 | 988 | 147119 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Bernard Rosner | 190 | 1162 | 147661 |
Stuart H. Orkin | 186 | 715 | 112182 |
Mark Hallett | 186 | 1170 | 123741 |
Ralph Weissleder | 184 | 1160 | 142508 |