For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
16
views
37
references
 Top references
cited by
139
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      488
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.

          Highlights

          • •

            hiPSC-derived astrocyte populations generated from 42 NPC lines

          • •

            Transcriptomic analysis shows hiPSC-astrocytes resemble primary human astrocytes

          • •

            hiPSC-astrocyte transcription is consistent with a non-reactive state

          • •

            hiPSC-astrocytes undergo inflammatory response and enhance microglial phagocytosis

          Abstract

          Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Uniquely hominid features of adult human astrocytes.

          Nancy Ann Oberheim, Takahiro Takano, Xiaoning Han … (2009)
          Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca(2+) waves with a speed of 36 microm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca(2+) in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
          Article 0 comments Cited 463 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Regulation of synaptic connectivity by glia.

            Cagla Eroglu, Ben A. Barres (2010)
            The human brain contains more than 100 trillion (10(14)) synaptic connections, which form all of its neural circuits. Neuroscientists have long been interested in how this complex synaptic web is weaved during development and remodelled during learning and disease. Recent studies have uncovered that glial cells are important regulators of synaptic connectivity. These cells are far more active than was previously thought and are powerful controllers of synapse formation, function, plasticity and elimination, both in health and disease. Understanding how signalling between glia and neurons regulates synaptic development will offer new insight into how the nervous system works and provide new targets for the treatment of neurological diseases.
            Article 0 comments Cited 267 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen.

              Miao Xu, Emily M Lee, Zhexing Wen … (2016)
              In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures. Ten structurally unrelated inhibitors of cyclin-dependent kinases inhibited ZIKV replication. Niclosamide, a category B anthelmintic drug approved by the US Food and Drug Administration, also inhibited ZIKV replication. Finally, combination treatments using one compound from each category (neuroprotective and antiviral) further increased protection of human neural progenitors and astrocytes from ZIKV-induced cell death. Our results demonstrate the efficacy of this screening strategy and identify lead compounds for anti-ZIKV drug development.
              Article 0 comments Cited 267 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Alison M. Goate
                Kristen J. Brennand
                Journal
                Journal ID (nlm-ta): Stem Cell Reports
                Journal ID (iso-abbrev): Stem Cell Reports
                Title: Stem Cell Reports
                Publisher: Elsevier
                ISSN (Electronic): 2213-6711
                Publication date PMC-release: 27 July 2017
                Publication date Collection: 08 August 2017
                Publication date (Electronic): 27 July 2017
                Volume: 9
                Issue: 2
                Pages: 600-614
                Affiliations
                [1 ]Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA
                [2 ]Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA
                [3 ]Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA
                [4 ]Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA
                [5 ]New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA
                [6 ]Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA
                Author notes
                [∗ ]Corresponding author alison.goate@ 123456mssm.edu
                [∗∗ ]Corresponding author kristen.brennand@ 123456mssm.edu
                [7]

                These authors contributed equally

                Article
                Publisher ID: S2213-6711(17)30281-3
                DOI: 10.1016/j.stemcr.2017.06.018
                PMC ID: 5550034
                PubMed ID: 28757165
                SO-VID: c4057dd1-ff38-4502-99b7-44259ed0b0c4
                Copyright © © 2017 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 30 April 2017
                Date revision received : 28 June 2017
                Date accepted : 29 June 2017
                Categories
                Subject: Article

                Keywords: human induced pluripotent stem cell,ipsc,astrocyte
                Data availability:
                Keywords: human induced pluripotent stem cell, ipsc, astrocyte

                Comments

                Comment on this article

                scite_

                Similar content488

                See all similar

                Cited by136

                See all cited by

                Most referenced authors907

                See all reference authors