A5044915933- Pluripotent Stem Cells Research
- Renal and related cancers
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- Tissue Engineering and Regenerative Medicine
- Hippo pathway signaling and YAP/TAZ
- FOXO transcription factor regulation
- Developmental Biology and Gene Regulation
- dental development and anomalies
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- TGF-β signaling in diseases
- Genetics and Physical Performance
- Interdisciplinary Research and Collaboration
- Empathy and Medical Education
- Pancreatic and Hepatic Oncology Research
- Medical Research and Treatments
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neural Engineering
- Mechanisms of cancer metastasis
- Immune cells in cancer
- Academic Publishing and Open Access
- Liver physiology and pathology
- Connective tissue disorders research
New York University
2022-2023
New York University Langone Orthopedic Hospital
2023
Memorial Sloan Kettering Cancer Center
2016-2021
Wellcome/MRC Cambridge Stem Cell Institute
2017-2021
Medical Research Council
2017-2021
University of Cambridge
2017-2021
Wellcome Trust
2021
University of Copenhagen
2013-2017
Google (United States)
2014
MRC Centre for Regenerative Medicine
2013
Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition totipotency, when individual blastomeres can make all lineages, to pluripotency, they competent only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) thought represent an embryonically restricted ground state. However, we observed heterogeneous expression extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior epiblast commitment....
During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of embryo. Similarly, human pluripotent stem (PSCs) undergo organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for human, we developed a mouse PSC micropattern system and, with direct comparisons to embryos, reveal robust distinct regional identities. BMP, WNT, ACTIVIN FGF directed epiblast-like an epithelial-to-mesenchymal transition...
TGF-β receptors phosphorylate SMAD2 and SMAD3 transcription factors, which then form heterotrimeric complexes with SMAD4 cooperate context-specific factors to activate target genes. Here we provide biochemical structural evidence showing that binding of DNA depends on the conformation E3 insert, a element unique previously thought render unable bind DNA. Based this finding, further delineate signal transduction by defining distinct roles for forkhead pioneer factor FOXH1 as partner in...
Embryonic stem cells (ESCs) are pluripotent cell lines that can be maintained indefinitely in an early developmental state. ESC culture conditions almost all require the cytokine LIF to maintain self-renewal. As ESCs not homogeneous, but contain multiple populations reminiscent of blastocyst, identifying target is necessary understand propagation pluripotency. We recently found acts under self-renewing stimulate fraction express extraembryonic markers, has little impact on gene expression....
Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, environmental interactions to generate physical arrangement blastocyst with precise timing. However, this process occurs in absence maternal information presence transcriptional stochasticity. How does preimplantation embryo ensure robust, reproducible context? utilizes a versatile toolbox that includes complex intracellular networks...
Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess impact of derivation and culture conditions on both functional potency ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i) or with knockout serum replacement (KOSR), but not serum, can generate high-level chimeras regardless how these were derived. showed a correlation early embryos (E1.5-E3.5) contributed to development 2-cell stage....
ABSTRACT Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance repair. Deciphering the molecular mechanisms that regulate their function is crucial for successful generation application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary sufficient periosteal cell function. genes transcriptionally enriched in overexpression more committed progenitors drives reprogramming a naïve, self-renewing cell-like state. Crucially,...
Skeletal stem and progenitor cells (SSPCs) perform bone maintenance repair. With age, they produce fewer osteoblasts more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed Notch signaling becomes elevated in SSPCs during aging. To examine the role increased activity, we deleted Nicastrin, an essential pathway component, vivo. Middle-aged conditional knockout mice...
During early mammalian development, the pluripotent cells of embryo are exposed to a combination signals that drive exit from pluripotency and germ layer differentiation. At same time, small population give rise primordial (PGCs), precursors sperm egg, which pass on heritable genetic information next generation. Despite importance PGCs, it remains unclear how they first segregated soma, if this involves distinct responses their signaling environment. To investigate question, we mapped BMP,...
Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor acting downstream of RAS signaling. Rreb1 has been implicated in cancer and Noonan-like RASopathies. However, little known about its role mammalian non-disease states. Here, we show that essential for mouse embryonic development. Loss led to reduction the expression vasculogenic factors, cardiovascular defects, lethality. During gastrulation, absence also resulted upregulation cytoskeleton-associated...
Abstract During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of embryo. Similarly, human pluripotent stem (PSCs) undergo organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for human, we developed a mouse PSC micropattern system and, with direct comparisons to embryos, reveal robust distinct regional identities. BMP, WNT, ACTIVIN FGF directed epiblast-like an epithelial-to-mesenchymal...
Abstract Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor downstream of RAS signaling. Rreb1 has been implicated in cancer but little known about its role mammalian non-disease states. Here, we found that essential for mouse embryonic development. Loss led to reduction the expression vasculogenesis factors, cardiovascular defects and lethality. During gastrulation, absence also resulted upregulation cytoskeleton-associated genes, change organization...