Author
Juliana Brown
Other affiliations: Howard Hughes Medical Institute, Broad Institute, Boston Children's Hospital
Bio: Juliana Brown is an academic researcher from Harvard University. The author has contributed to research in topics: Neocortex & Cellular differentiation. The author has an hindex of 11, co-authored 15 publications receiving 3019 citations. Previous affiliations of Juliana Brown include Howard Hughes Medical Institute & Broad Institute.
Papers
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TL;DR: This work introduces a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest and suggests that terminally differentiated β-cells retain a significant proliferative capacity in vivo and casts doubt on the idea that adult stem cells have a significant role in β-cell replenishment.
Abstract: How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic beta-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment.
2,103 citations
TL;DR: Results indicate the stage at which each progenitor population is restricted to a particular fate and provide markers for isolating progenitors to study their growth, differentiation, and the genes necessary for their development.
239 citations
TL;DR: This multifaceted study paired high-throughput purification of pyramidal neuron subclasses with deep profiling of spatiotemporal transcriptional dynamics during corticogenesis to resolve lineage choice decisions and uncovered numerous long noncoding RNAs with restricted temporal and cell-type-specific expression.
220 citations
TL;DR: The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders.
Abstract: Neuropsychiatric disorders such as autism spectrum disorder (ASD), schizophrenia (SCZ) and bipolar disorder (BPD) are of great societal and medical importance, but the complexity of these diseases and the challenges of modeling the development and function of the human brain have made these disorders difficult to study experimentally The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders and for understanding the contribution of individual risk variants and complex genetic background to human pathology Here we discuss the advantages, limitations and future applications of human brain organoids as in vitro models of neuropsychiatric disease
217 citations
TL;DR: Notch receptors are involved in regulating the balance between cell differentiation and stem cell proliferation during the development of numerous tissues and coexpression with HES 1 suggests that the Notch 1 pathway is activated.
138 citations
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TL;DR: This study identifies a specific combination of three transcription factors (Ngn3) Pdx1 and Mafa that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble β-cells, and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
Abstract: One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
1,990 citations
Cornell University1, University of Pennsylvania2, NewYork–Presbyterian Hospital3, Hannover Medical School4, Rockefeller University5, National Taiwan University6, Oslo University Hospital7, University of Oslo8, Memorial Sloan Kettering Cancer Center9, Eppley Institute for Research in Cancer and Allied Diseases10, University of Nebraska Medical Center11
TL;DR: It is shown that PDAC-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden and suggests that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PDAC liver metastasis.
Abstract: Lyden and colleagues report that pancreatic cancer-derived exosomes induce a pre-metastatic niche in the liver by promoting TGFβ secretion from Kupffer cells, leading to fibronectin production in hepatic stellate cells and macrophage recruitment.
1,973 citations
Wellcome Trust Centre for Human Genetics1, University of Michigan2, University of Oxford3, Brigham and Women's Hospital4, Harvard University5, Massachusetts Institute of Technology6, Lund University7, Steno Diabetes Center8, University of Southern California9, National Institutes of Health10, Health Science University11, Novartis12, Ninewells Hospital13, University of Exeter14, University of Düsseldorf15, Queen Mary University of London16, Glostrup Hospital17, deCODE genetics18, University of Eastern Finland19, University of Cambridge20, Aarhus University21, University of North Carolina at Chapel Hill22, Norwegian University of Science and Technology23, Wellcome Trust Sanger Institute24, University of Bristol25, University of Helsinki26, Newcastle University27
TL;DR: The results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D, and detect at least six previously unknown loci with robust evidence for association.
Abstract: Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
1,872 citations
TL;DR: It is suggested that inflammation enhances cancer progression in part by facilitating EMT and entry into the circulation and tagged cells invaded and entered the bloodstream unexpectedly early, before frank malignancy could be detected by rigorous histologic analysis.
1,777 citations
TL;DR: In this article, the authors present an analysis of development in the context of the World Wide Web, with a focus on the first three stages of the development process and the first stage of the Internet.
Abstract: Analysis of Development Edited by Prof Benjamin H Willier, Prof Paul A Weiss and Prof Viktor Hamburger Pp xii + 735 (Philadelphia and London: W B Saunders Company, 1955) 105s
1,245 citations