A5041566748- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Renal and related cancers
- Genomics and Chromatin Dynamics
- 3D Printing in Biomedical Research
- Genetics and Neurodevelopmental Disorders
- Animal Genetics and Reproduction
- Genetic Syndromes and Imprinting
- Sperm and Testicular Function
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Ovarian function and disorders
- Erythrocyte Function and Pathophysiology
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Reproductive System and Pregnancy
- Virus-based gene therapy research
- Birth, Development, and Health
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Pancreatic function and diabetes
- Vector-Borne Animal Diseases
Whitehead Institute for Biomedical Research
2015-2024
Northwestern University
2023
University of Connecticut
2023
Massachusetts Institute of Technology
2007-2023
University of Alabama at Birmingham
2007
Tufts University
2003-2007
Beth Israel Deaconess Medical Center
2000
It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell–like state by introducing combinations of four transcription factors. However, the therapeutic potential such induced pluripotent (iPS) cells remained undefined. By using a humanized sickle cell anemia model, we show mice rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved correction hemoglobin allele...
Directed reprogramming of somatic cells by defined factors provides a novel method for the generation patient-specific stem with potential to bypass both practical and ethical concerns associated cell nuclear transfer (SCNT) human embryonic (hES) cells. Although induced pluripotent (iPS) has proven robust technology in mouse human, major impediment use iPS therapeutic purposes been viral-based delivery because multiple proviral integrations pose danger insertional mutagenesis. Here we report...
Recent studies have aimed to convert cultured human pluripotent cells a naive state, but it remains unclear what extent the resulting recapitulate in vivo pluripotency. Here we propose set of molecular criteria for evaluating state by comparing embryo. We show that transcription transposable elements provides sensitive measure concordance between stem and early development. also induction is accompanied genome-wide DNA hypomethylation, which reversible except at imprinted genes, X chromosome...
Ectopic expression of defined transcription factors can reprogram somatic cells to induced pluripotent stem (iPS) cells, but the utility iPS is hampered by use viral delivery systems. Small molecules offer an alternative replace virally transduced with chemical signaling cues responsible for reprogramming. In this report we describe a small-molecule screening platform applied identify compounds that functionally reprogramming factor Klf4. A series scaffolds were identified activate Nanog in...
Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair resolution or direct localization. Here, we describe in situ sequencing (IGS), a method for simultaneously imaging genomes within intact biological samples. We applied IGS to human fibroblasts early mouse embryos, spatially localizing thousands genomic loci individual nuclei. Using these data, characterized parent-specific...
Embryogenesis requires the timely and coordinated activation of developmental regulators. It has been suggested that recently discovered class histone demethylases (UTX JMJD3) specifically target repressive H3K27me3 modification play an important role in “bivalent” genes response to specific cues. To determine requirements for UTX pluripotency development, we have generated Utx -null ES cells mutant mice. The loss had a profound effect during embryogenesis. embryos reduced somite counts,...
Mir-290 through mir-295 ( mir-290–295 ) is a mammalian-specific microRNA (miRNA) cluster that, in mice, expressed specifically early embryos and embryonic germ cells. Here, we show that plays important roles development as indicated by the partially penetrant lethality of mutant embryos. In addition, surviving -deficient embryos, female but not male fertility compromised. This impairment arises from defect migrating primordial cells occurs equally animals. Male −/− due to extended...
Abstract Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 genome editing. However, the events that lead to these karyotypic changes in embryos after Cas9-treatment remain unknown. Here, using imaging and single-cell sequencing of 8-cell stage embryos, we track both spontaneous Cas9-induced karyotype aberrations through first three divisions embryonic development. We observe generation abnormal structures nucleus arise a consequence errors mitosis, including...
Compounds with estrogenic activity can affect reproductive function in mammals. This study investigated possible effects of 17beta-estradiol (E(2)) and three weakly environmental estrogens on mammalian sperm capacitation fertilizing ability vitro.Uncapacitated capacitated mouse suspensions were incubated for 30 min the presence E(2), genistein (Gen), 8-prenylnaringenin (8-PN) nonylphenol (NP), then assessed using chlortetracycline (CTC) fluorescence analysis. In addition, treated...
Regulatory T cells (Tregs) modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, we show that Tregs maintain the tolerogenic state of testis epididymis, where sperm are produced mature. We found Treg depletion induces severe autoimmune orchitis epididymitis, manifested by an exacerbated cell infiltration [CD4 cells, monocytes, mononuclear phagocytes (MPs)] development...