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  • 1
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    Immunogenetics. Chromatin state dynamics during blood formation (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-08-12
    Description: Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of homogeneous differentiation intermediates. We developed a high-sensitivity indexing-first chromatin immunoprecipitation approach to profile the dynamics of four chromatin modifications across 16 stages of hematopoietic differentiation. We identify 48,415 enhancer regions and characterize their dynamics. We find that lineage commitment involves de novo establishment of 17,035 lineage-specific enhancers. These enhancer repertoire expansions foreshadow transcriptional programs in differentiated cells. Combining our enhancer catalog with gene expression profiles, we elucidate the transcription factor network controlling chromatin dynamics and lineage specification in hematopoiesis. Together, our results provide a comprehensive model of chromatin dynamics during development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412442/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lara-Astiaso, David -- Weiner, Assaf -- Lorenzo-Vivas, Erika -- Zaretsky, Irina -- Jaitin, Diego Adhemar -- David, Eyal -- Keren-Shaul, Hadas -- Mildner, Alexander -- Winter, Deborah -- Jung, Steffen -- Friedman, Nir -- Amit, Ido -- 1P50HG006193/HG/NHGRI NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):943-9. doi: 10.1126/science.1256271. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. ; Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel. ; Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il. ; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103404" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/genetics ; Chromatin/*metabolism ; Chromatin Immunoprecipitation/methods ; *Enhancer Elements, Genetic ; Female ; Gene Expression Profiling ; *Gene Expression Regulation ; Hematopoiesis/*genetics ; Hematopoietic Stem Cells/cytology/*metabolism ; Histones/chemistry/metabolism ; Mice ; Transcription Factors/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-02-18
    Description: In multicellular organisms, biological function emerges when heterogeneous cell types form complex organs. Nevertheless, dissection of tissues into mixtures of cellular subpopulations is currently challenging. We introduce an automated massively parallel single-cell RNA sequencing (RNA-seq) approach for analyzing in vivo transcriptional states in thousands of single cells. Combined with unsupervised classification algorithms, this facilitates ab initio cell-type characterization of splenic tissues. Modeling single-cell transcriptional states in dendritic cells and additional hematopoietic cell types uncovers rich cell-type heterogeneity and gene-modules activity in steady state and after pathogen activation. Cellular diversity is thereby approached through inference of variable and dynamic pathway activity rather than a fixed preprogrammed cell-type hierarchy. These data demonstrate single-cell RNA-seq as an effective tool for comprehensive cellular decomposition of complex tissues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412462/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412462/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaitin, Diego Adhemar -- Kenigsberg, Ephraim -- Keren-Shaul, Hadas -- Elefant, Naama -- Paul, Franziska -- Zaretsky, Irina -- Mildner, Alexander -- Cohen, Nadav -- Jung, Steffen -- Tanay, Amos -- Amit, Ido -- P50 HG006193/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):776-9. doi: 10.1126/science.1247651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers ; Dendritic Cells/metabolism ; Female ; Hematopoiesis/genetics ; Mice, Inbred C57BL ; RNA, Messenger/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; Spleen/metabolism ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Induction of CD4 T cell memory by local cellular collectivity (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-06-15
    Description: Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4 + T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses.
    Keywords: Immunology, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types (2014)
    American Association for the Advancement of Science
    Details
    Publication Date: 2014-02-13
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science
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