ORCID Profile
0000-0002-7400-7438
Current Organisation
Icahn School of Medicine at Mount Sinai
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Publisher: Elsevier BV
Date: 07-2021
Publisher: Cold Spring Harbor Laboratory
Date: 07-04-2021
DOI: 10.1101/2021.04.07.438755
Abstract: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. To comprehensively map cell lineages in the healthy developing, pediatric and adult human gut from ten distinct anatomical regions, as well as draining lymph nodes, we used singlecell RNA-seq and VDJ analysis of roughly one third of a million cells. This reveals the presence of BEST4+ absorptive cells throughout the human intestinal tract, demonstrating the existence of this cell type beyond the colon for the first time. Furthermore, we implicate IgG sensing as a novel function of intestinal tuft cells, and link these cells to the pathogenesis of inflammatory bowel disease. We define novel glial and neuronal cell populations in the developing enteric nervous system, and predict cell-type specific expression of Hirschsprung’s disease-associated genes. Finally, using a systems approach, we identify key cell players across multiple cell lineages driving secondary lymphoid tissue formation in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. These data provide an unprecedented catalogue of intestinal cells, and new insights into cellular programs in development, homeostasis and disease.
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2023
DOI: 10.1101/2023.03.08.531713
Abstract: Single-cell data analysis can infer dynamic changes in cell populations, for ex le across time, space or in response to perturbation. To compare these dynamics between two conditions, trajectory alignment via dynamic programming (DP) optimization is frequently used, but is limited by assumptions such as a definite existence of a match. Here we describe Genes2Genes , a Bayesian information-theoretic DP framework for aligning single-cell trajectories. Genes2Genes overcomes current limitations and is able to capture sequential matches and mismatches between a reference and a query at single gene resolution, highlighting distinct clusters of genes with varying patterns of expression dynamics. Across both real world and simulated datasets, Genes2Genes accurately captured different alignment patterns, demonstrated its utility in disease cell state trajectory analysis, and revealed that T cells differentiated in vitro matched to an immature in vivo state while lacking the final TNFa signaling. This use case demonstrates that precise trajectory alignment can pinpoint ergence from the in vivo system, thus guiding the optimization of in vitro culture conditions.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2021
DOI: 10.1038/S41591-021-01329-2
Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts ( CD16 + C1QA/B/C + ) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34 + hematopoietic stem rogenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8 + T cells and an increased ratio of CD8 + effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2021
Publisher: Springer Science and Business Media LLC
Date: 08-09-2021
DOI: 10.1038/S41586-021-03852-1
Abstract: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2022
DOI: 10.1038/S41587-021-01139-4
Abstract: Spatial transcriptomic technologies promise to resolve cellular wiring diagrams of tissues in health and disease, but comprehensive mapping of cell types in situ remains a challenge. Here we present сell2location, a Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of erse tissues. Cell2location accounts for technical sources of variation and borrows statistical strength across locations, thereby enabling the integration of single-cell and spatial transcriptomics with higher sensitivity and resolution than existing tools. We assessed cell2location in three different tissues and show improved mapping of fine-grained cell types. In the mouse brain, we discovered fine regional astrocyte subtypes across the thalamus and hypothalamus. In the human lymph node, we spatially mapped a rare pre-germinal center B cell population. In the human gut, we resolved fine immune cell populations in lymphoid follicles. Collectively, our results present сell2location as a versatile analysis tool for mapping tissue architectures in a comprehensive manner.
Location: United States of America
Location: United States of America
No related grants have been discovered for Emma Dann.