Egli D.,New York Stem Cell Foundation Laboratory |
Akutsu H.,National Health Research Institute
Journal of Mammalian Ova Research
Women in Japan and elsewhere are increasingly delaying childbearing. The percentage of Japanese women giving birth to their first child at the age of 30 and above has increased from 28.9% in 1980 to 58.9% in 2009. As a result, women seeking to conceive one or more children increasingly do so when the effects of reproductive aging first become noticeable. Female fertility begins to decrease after 30 years of age, falls markedly after the age of 35 in association with an increased risk of complications during pregnancy and of chromosomal abnormalities in the offspring, and most women become infertile after the age of 40. In parallel, the number of assisted reproductive technology (ART) treatment cycles in Japan is steadily increasing, from 37,455 in 1997 to 190,613 in 2008, according to a survey by the Japan Society of Obstetrics and Gynecology. Because of the high emotional and social toll of infertility on couples and the demographic consequences of a decrease in fecundity, it is imperative to better understand the biology of reproductive aging. Here we review current knowledge about the decline of female fertility during aging and discuss the implications for infertility treatments. Source
Chan M.M.,The Broad Institute of MIT and Harvard |
Chan M.M.,Massachusetts Institute of Technology |
Smith Z.D.,The Broad Institute of MIT and Harvard |
Smith Z.D.,Harvard Stem Cell Institute |
And 8 more authors.
Enucleated oocytes have the distinctive ability to reprogram somatic nuclei back to totipotency. Here, we investigate genome-scale DNA methylation patterns after nuclear transfer and compare them to the dynamics at fertilization. We identify specific targets for DNA demethylation after nuclear transfer, such as germline-associated promoters, as well as unique limitations that include certain repetitive element classes. © 2012 Nature America, Inc. All rights reserved. Source
Egli D.,Harvard University |
Egli D.,Harvard Stem Cell Institute |
Egli D.,New York Stem Cell Foundation Laboratory |
Egli D.,Columbia University |
And 18 more authors.
Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation. © 2011 Macmillan Publishers Limited. All rights reserved. Source
Hua H.,New York Stem Cell Foundation Laboratory |
Hua H.,Columbia University |
Shang L.,New York Stem Cell Foundation Laboratory |
Martinez H.,New York Stem Cell Foundation Laboratory |
And 11 more authors.
Journal of Clinical Investigation
Diabetes is a disorder characterized by loss of β cell mass and/or β cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell-derived β cells recapitulate molecular-physiological phenotypes of a diabetic subject, we generated induced pluripotent stem cells (iPSCs) from subjects with maturity-onset diabetes of the young type 2 (MODY2), which is characterized by heterozygous loss of function of the gene encoding glucokinase (GCK). These stem cells differentiated into β cells with efficiency comparable to that of controls and expressed markers of mature β cells, including urocortin-3 and zinc transporter 8, upon transplantation into mice. While insulin secretion in response to arginine or other secretagogues was identical to that in cells from healthy controls, GCK mutant β cells required higher glucose levels to stimulate insulin secretion. Importantly, this glucose-specific phenotype was fully reverted upon gene sequence correction by homologous recombination. Our results demonstrate that iPSC-derived β cells reflect β cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on β cell function. Source
Nestor M.W.,New York Stem Cell Foundation Laboratory |
Nestor M.W.,The Hussman Institute for Autism |
Jacob S.,New York Stem Cell Foundation Laboratory |
Sun B.,New York Stem Cell Foundation Laboratory |
And 9 more authors.
American Journal of Physiology - Cell Physiology
Production and isolation of forebrain interneuron progenitors are essential for understanding cortical development and developing cell-based therapies for developmental and neurodegenerative disorders. We demonstrate production of a population of putative calretinin-positive bipolar interneurons that express markers consistent with caudal ganglionic eminence identities. Using serum-free embryoid bodies (SFEBs) generated from human inducible pluripotent stem cells (iPSCs), we demonstrate that these interneuron progenitors exhibit morphological, immunocytochemical, and electrophysiological hallmarks of developing cortical interneurons. Finally, we develop a fluorescence-activated cell-sorting strategy to isolate interneuron progenitors from SFEBs to allow development of a purified population of these cells. Identification of this critical neuronal cell type within iPSC-derived SFEBs is an important and novel step in describing cortical development in this iPSC preparation. © 2015 the American Physiological Society. Source