A5078655497- Pluripotent Stem Cells Research
- Renal and related cancers
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Hair Growth and Disorders
- Autophagy in Disease and Therapy
- Microtubule and mitosis dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- RNA modifications and cancer
- Reproductive Biology and Fertility
- Adenosine and Purinergic Signaling
- Molecular Biology Techniques and Applications
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Congenital heart defects research
- Skin and Cellular Biology Research
Icahn School of Medicine at Mount Sinai
2018-2023
Wellcome/MRC Cambridge Stem Cell Institute
2009-2021
Medical Research Council
2014-2021
University of Cambridge
2011-2020
The Gurdon Institute
2014
Wellcome Trust
2014
Goethe University Frankfurt
2009
Homeostasis of most adult tissues is maintained by balancing stem cell self-renewal and differentiation, but whether post-transcriptional mechanisms can regulate this process unknown. Here, we identify that an RNA methyltransferase (Misu/Nsun2) required to balance differentiation in skin. In the epidermis, found a defined sub-population hair follicle cells poised undergo lineage commitment, its depletion results enhanced quiescence aberrant differentiation. Our reveal methylation play...
The transcription factor Oct4 is required in vitro for establishment and maintenance of embryonic stem cells reprogramming somatic to pluripotency. In vivo, it prevents the ectopic differentiation early embryos into trophoblast. Here, we further explore role blastocyst formation specification epiblast versus primitive endoderm lineages using conditional genetic deletion. Experiments involving mouse deficient both maternal zygotic suggest that dispensable zygote formation, cleavage activation...
Myc-induced SUN domain–containing protein (Misu or NSun2) is a nucleolar RNA methyltransferase important for c-Myc–induced proliferation in skin, but the mechanisms by which Misu contributes to cell cycle progression are unknown. In this study, we demonstrate that translocates from nucleoli interphase spindle mitosis as an RNA–protein complex includes 18S ribosomal RNA. Functionally, depletion of caused multiple mitotic defects, including formation unstructured spindles, multipolar and...
Significance We used single-cell whole-genome transcriptional profiling and protein quantification to investigate the role of OCT4 in establishing pluripotency murine embryo. Surprisingly, most pluripotency-associated factors are induced normally null early blastocysts, apart from members STAT3 signaling pathway. Coincidentally, certain trophectoderm markers but not Cdx2 , which was previously implicated repress Pou5f1 vitro. This ectopic gene activation suggests a for maintaining chromatin...
Autophagy is a conserved metabolic pathway that central to many diseases. Recently, there has been lot of interest in targeting autophagy with small molecule inhibitors as possible therapeutic strategy. However, the compounds used for are nonselective. Here, we explored inhibition pancreatic cancer cells using established selective and discovered an unexpected link between progression through cell cycle. Our findings revealed treatments have different targets block replication activate other...
ABSTRACT A crucial aspect of embryology is relating the position individual cells to broader geometry embryo. classic example this first cell-fate decision mouse embryo, where interior become inner cell mass and exterior trophectoderm. Fluorescent labelling, imaging, quantification tissue-specific proteins have advanced our understanding dynamic process. However, instances arise these markers are either not available, or reliable, we left only with cells’ spatial locations. Therefore, a...
Abstract OCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and vitro . To determine how protects pluripotent lineage from differentiation into trophoblast, we used single cell transcriptomics quantitative immunofluorescence on blastocysts established differentially expressed genes pathways between control null cells. Activation most pluripotency-associated transcription factors early mouse inner mass appears independent OCT4, whereas JAK/STAT...
Abstract A crucial aspect of embryology is relating the position individual cells to broader geometry embryo. classic example this first cell-fate decision mouse embryo, where interior become inner cell mass and exterior trophectoderm. Fluorescent labelling, imaging, quantification tissue-specific proteins have advanced our understanding dynamic process. However instances arise these markers are either not available, or reliable, we left only with cells’ spatial locations. Therefore, a...