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Article ; Online: Generation of Mammalian Astrocyte Functional Heterogeneity.

Bartels, Theresa / Rowitch, David H / Bayraktar, Omer Ali

Cold Spring Harbor perspectives in biology

2024

Abstract: Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development ... ...

Abstract	Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development into specialized regions into adulthood. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia and/or local neuron inductive cues. Here, we review evidence for regionally encoded functions of astrocytes to provide an integrated concept on lineage origins and heterogeneity to understand regional brain organization, as well as emerging technologies to identify and further investigate novel roles for astrocytes.
Language	English
Publishing date	2024-05-01
Publishing country	United States
Document type	Journal Article
ISSN	1943-0264
ISSN (online)	1943-0264
DOI	10.1101/cshperspect.a041351
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Article ; Online: Astrocytes: The Final Frontier….

Kelley, Kevin W / Rowitch, David H

Neuron

2016 Volume 89, Issue 1, Page(s) 1–2

Abstract: In this issue of Neuron, Zhang et al. (2016) develop a novel approach to generate populations of human astrocytes to uncover their uniquely human traits. ...

Abstract	In this issue of Neuron, Zhang et al. (2016) develop a novel approach to generate populations of human astrocytes to uncover their uniquely human traits.
MeSH term(s)	Animals ; Astrocytes/cytology ; Brain/cytology ; Humans ; Microglia/cytology ; Neurons/cytology ; Oligodendroglia/cytology
Language	English
Publishing date	2016-01-06
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2015.12.030
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: The Role of the Neurointensive Care Nursery for Neonatal Encephalopathy.

Glass, Hannah C / Rowitch, David H

Clinics in perinatology

2016 Volume 43, Issue 3, Page(s) 547–557

Abstract: Neonatal encephalopathy due to intrapartum events is estimated at 1 to 2 per 1000 live births in high-income countries. Outcomes have improved over the past decade due to implementation of therapeutic hypothermia, the only clinically available ... ...

Abstract	Neonatal encephalopathy due to intrapartum events is estimated at 1 to 2 per 1000 live births in high-income countries. Outcomes have improved over the past decade due to implementation of therapeutic hypothermia, the only clinically available neuroprotective strategy for hypoxic-ischemic encephalopathy. Neonatal encephalopathy is the most common condition treated within a neonatal neurocritical care unit. Neonates with encephalopathy benefit from a neurocritical care approach due to prevention of secondary brain injury through attention to basic physiology, earlier recognition and treatment of neurologic complications, consistent management using guidelines and protocols, and use of optimized teams at dedicated referral centers.
MeSH term(s)	Cooperative Behavior ; Hospital Units ; Humans ; Hypoxia-Ischemia, Brain/therapy ; Infant, Newborn ; Intensive Care Units, Neonatal ; Neonatologists ; Neurologists ; Neurology
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	193116-7
ISSN	1557-9840 ; 0095-5108
ISSN (online)	1557-9840
ISSN	0095-5108
DOI	10.1016/j.clp.2016.04.011
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Article ; Online: Diversity and Function of Glial Cell Types in Multiple Sclerosis.

Schirmer, Lucas / Schafer, Dorothy P / Bartels, Theresa / Rowitch, David H / Calabresi, Peter A

Trends in immunology

2021 Volume 42, Issue 3, Page(s) 228–247

Abstract: Glial subtype diversity is an emerging topic in neurobiology and immune-mediated neurological diseases such as multiple sclerosis (MS). We discuss recent conceptual and technological advances that allow a better understanding of the transcriptomic and ... ...

Abstract	Glial subtype diversity is an emerging topic in neurobiology and immune-mediated neurological diseases such as multiple sclerosis (MS). We discuss recent conceptual and technological advances that allow a better understanding of the transcriptomic and functional heterogeneity of oligodendrocytes (OLs), astrocytes, and microglial cells under inflammatory-demyelinating conditions. Recent single cell transcriptomic studies suggest the occurrence of novel homeostatic and reactive glial subtypes and provide insight into the molecular events during disease progression. Multiplexed RNA in situ hybridization has enabled 'mapping back' dysregulated gene expression to glial subtypes within the MS lesion microenvironment. These findings suggest novel homeostatic and reactive glial-cell-type functions both in immune-related processes and neuroprotection relevant to understanding the pathology of MS.
MeSH term(s)	Astrocytes ; Humans ; Microglia ; Multiple Sclerosis ; Neuroglia ; Oligodendroglia
Language	English
Publishing date	2021-02-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2021.01.005
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 2: Show issues

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Article ; Online: New Recipes for Myelinating Oligodendrocytes.

Nobuta, Hiroko / Stockley, John H / Rowitch, David H

Cell stem cell

2018 Volume 23, Issue 4, Page(s) 464–465

Abstract: While myelinating oligodendrocytes are attractive candidates for cell-based regenerative therapies, producing them in adequate quantities and regulation of progenitor differentiation pathways has proven limiting. Recently, Hubler et al. (2018) and ... ...

Abstract	While myelinating oligodendrocytes are attractive candidates for cell-based regenerative therapies, producing them in adequate quantities and regulation of progenitor differentiation pathways has proven limiting. Recently, Hubler et al. (2018) and Madhavan et al. (2018) generated cerebral organoids with myelinating oligodendrocytes and manipulated sterol pathway small molecules to promote myelin synthesis.
MeSH term(s)	Cell Differentiation ; Humans ; Myelin Sheath ; Oligodendroglia
Language	English
Publishing date	2018-11-20
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2018.09.011
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Zs.A 6589: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 75: Show issues

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Article ; Online: Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion.

Tanabe, Koji / Nobuta, Hiroko / Yang, Nan / Ang, Cheen Euong / Huie, Philip / Jordan, Sacha / Oldham, Michael C / Rowitch, David H / Wernig, Marius

Development (Cambridge, England)

2022 Volume 149, Issue 20

Abstract: Oligodendrocytes, the myelinating cells of the central nervous system, possess great potential for disease modeling and cell transplantation-based therapies for leukodystrophies. However, caveats to oligodendrocyte differentiation protocols ( Ehrlich et ... ...

Abstract	Oligodendrocytes, the myelinating cells of the central nervous system, possess great potential for disease modeling and cell transplantation-based therapies for leukodystrophies. However, caveats to oligodendrocyte differentiation protocols ( Ehrlich et al., 2017; Wang et al., 2013; Douvaras and Fossati, 2015) from human embryonic stem and induced pluripotent stem cells (iPSCs), which include slow and inefficient differentiation, and tumorigenic potential of contaminating undifferentiated pluripotent cells, are major bottlenecks towards their translational utility. Here, we report the rapid generation of human oligodendrocytes by direct lineage conversion of human dermal fibroblasts (HDFs). We show that the combination of the four transcription factors OLIG2, SOX10, ASCL1 and NKX2.2 is sufficient to convert HDFs to induced oligodendrocyte precursor cells (iOPCs). iOPCs resemble human primary and iPSC-derived OPCs based on morphology and transcriptomic analysis. Importantly, iOPCs can differentiate into mature myelinating oligodendrocytes in vitro and in vivo. Finally, iOPCs derived from patients with Pelizaeus Merzbacher disease, a hypomyelinating leukodystrophy caused by mutations in the proteolipid protein 1 (PLP1) gene, showed increased cell death compared with iOPCs from healthy donors. Thus, human iOPCs generated by direct lineage conversion represent an attractive new source for human cell-based disease models and potentially myelinating cell grafts.
MeSH term(s)	Cell Differentiation/physiology ; Fibroblasts ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Oligodendroglia/metabolism ; Pelizaeus-Merzbacher Disease/genetics ; Pelizaeus-Merzbacher Disease/metabolism ; Pelizaeus-Merzbacher Disease/therapy
Language	English
Publishing date	2022-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.199723
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Ub I Zs.183: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 91: Show issues

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Article ; Online: The neurointensive nursery: concept, development, and insights gained.

Glass, Hannah C / Ferriero, Donna M / Rowitch, David H / Shimotake, Thomas K

Current opinion in pediatrics

2019 Volume 31, Issue 2, Page(s) 202–209

Abstract: Purpose of review: With the advent of therapeutic hypothermia for treatment of hypoxic ischemic encephalopathy, and improvements in neuroimaging and bedside neuromonitoring, a new era of neonatal brain-focused care has emerged in recent years. We ... ...

Abstract	Purpose of review: With the advent of therapeutic hypothermia for treatment of hypoxic ischemic encephalopathy, and improvements in neuroimaging and bedside neuromonitoring, a new era of neonatal brain-focused care has emerged in recent years. We describe the development of the first neurointensive care nursery (NICN) as a model for comanagement of neonates with identified neurologic risk factors by a multidisciplinary team constituted of neurologists, neonatologists, specialized nurses, and others with the goal of optimizing management, preventing secondary injury and maximizing long-term outcomes. Recent findings: Optimizing brain metabolic environment and perfusion and preventing secondary brain injury are key to neurocritical care. This includes close management of temperature, blood pressure, oxygenation, carbon dioxide, and glucose levels. Early developmental interventions and involvement of physical and occupational therapy provide additional assessment information. Finally, long-term follow-up is essential for any neurocritical care program. Summary: The NICN model aims to optimize evidence-based care of infants at risk for neurologic injury. Results from ongoing hypothermia and neuroprotective trials are likely to yield additional treatments. New technologies, such as functional MRI, continuous neurophysiological assessment, and whole genomic approaches to rapid diagnosis may further enhance clinical protocols and neonatal precision medicine. Importantly, advances in neurocritical care improve our ability to provide comprehensive information when counseling families. Long-term follow-up data will determine if the NICN/Neuro-NICU provides enduring benefit to infants at risk for neurologic injury.
MeSH term(s)	Brain ; Humans ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain/prevention & control ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Neurology/trends
Language	English
Publishing date	2019-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1049374-8
ISSN	1531-698X ; 1040-8703
ISSN (online)	1531-698X
ISSN	1040-8703
DOI	10.1097/MOP.0000000000000733
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Zs.A 3049: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
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Article ; Online: A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression.

Ghosh, Tanay / Almeida, Rafael G / Zhao, Chao / Mannioui, Abdelkrim / Martin, Elodie / Fleet, Alex / Chen, Civia Z / Assinck, Peggy / Ellams, Sophie / Gonzalez, Ginez A / Graham, Stephen C / Rowitch, David H / Stott, Katherine / Adams, Ian / Zalc, Bernard / Goldman, Nick / Lyons, David A / Franklin, Robin J M

Cell

2024 Volume 187, Issue 4, Page(s) 814–830.e23

Abstract: Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more ... ...

Abstract	Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.
MeSH term(s)	Animals ; Gene Expression ; Myelin Sheath/metabolism ; Oligodendroglia/metabolism ; Retroelements/genetics ; RNA/metabolism ; Zebrafish/genetics ; Anura
Chemical Substances	Retroelements ; RNA (63231-63-0)
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2024.01.011
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: Evolving concepts of gliogenesis: a look way back and ahead to the next 25 years.

Freeman, Marc R / Rowitch, David H

Neuron

2013 Volume 80, Issue 3, Page(s) 613–623

Abstract: Glial cells are present in all organisms with a CNS and, with increasing brain complexity, glial cells have undergone substantive increases in cell number, diversity, and functions. Invertebrates, such as Drosophila, possess glial subtypes with ... ...

Abstract	Glial cells are present in all organisms with a CNS and, with increasing brain complexity, glial cells have undergone substantive increases in cell number, diversity, and functions. Invertebrates, such as Drosophila, possess glial subtypes with similarity to mammalian astrocytes in their basic morphology and function, representing fertile ground for unraveling fundamental aspects of glial biology. Although glial subtypes in simple organisms may be relatively homogenous, emerging evidence suggests the possibility that mammalian astrocytes might be highly diversified to match the needs of local neuronal subtypes. In this Perspective, we review classic and new roles identified for astrocytes and oligodendrocytes by recent studies. We propose that delineating genetic and developmental programs across species will be essential to understand the core functions of glia that allow enhanced neuronal function and to achieve new insights into glial roles in higher-order brain function and neurological disease.
MeSH term(s)	Animals ; Biological Evolution ; Cell Differentiation/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Neuroglia/classification ; Neuroglia/physiology ; Neurosciences/history ; Neurosciences/trends
Language	English
Publishing date	2013-10-04
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2013.10.034
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Neuroprotective effects of Sonic hedgehog agonist SAG in a rat model of neonatal stroke.

Nguyen, Vien / Chavali, Manideep / Larpthaveesarp, Amara / Kodali, Srikirti / Gonzalez, Ginez / Franklin, Robin J M / Rowitch, David H / Gonzalez, Fernando

Pediatric research

2021 Volume 90, Issue 6, Page(s) 1161–1170

Abstract: Background: Neonatal stroke affects 1 in 2800 live births and is a major cause of neurological injury. The Sonic hedgehog (Shh) signaling pathway is critical for central nervous system (CNS) development and has neuroprotective and reparative effects in ... ...

Abstract	Background: Neonatal stroke affects 1 in 2800 live births and is a major cause of neurological injury. The Sonic hedgehog (Shh) signaling pathway is critical for central nervous system (CNS) development and has neuroprotective and reparative effects in different CNS injury models. Previous studies have demonstrated beneficial effects of small molecule Shh-Smoothened agonist (SAG) against neonatal cerebellar injury and it improves Down syndrome-related brain structural deficits in mice. Here we investigated SAG neuroprotection in rat models of neonatal ischemia-reperfusion (stroke) and adult focal white matter injury. Methods: We used transient middle cerebral artery occlusion at P10 and ethidium bromide (EB) injection in adult rats to induce damage. Following surgery and SAG or vehicle treatment, we analyzed tissue loss, cell proliferation and fate, and behavioral outcome. Results: We report that a single dose of SAG administered following neonatal stroke preserved brain volume, reduced gliosis, enhanced oligodendrocyte progenitor cell (OPC) and EC proliferation, and resulted in long-term cognitive improvement. Single-dose SAG also promoted proliferation of OPCs following focal demyelination in the adult rat. Conclusions: These findings indicate benefit of one-time SAG treatment post insult in reducing brain injury and improving behavioral outcome after experimental neonatal stroke. Impact: A one-time dose of small molecule Sonic hedgehog agonist protected against neonatal stroke and improved long-term behavioral outcomes in a rat model. This study extends the use of Sonic hedgehog in treating developing brain injury, previously shown in animal models of Down syndrome and cerebellar injury. Sonic hedgehog agonist is one of the most promising therapies in treating neonatal stroke thanks to its safety profile and low dosage.
MeSH term(s)	Animals ; Behavior, Animal ; Cell Proliferation ; Disease Models, Animal ; Hedgehog Proteins/antagonists & inhibitors ; Humans ; Infant, Newborn ; Infarction, Middle Cerebral Artery/complications ; Mice ; Neuroprotective Agents/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Small Molecule Libraries/therapeutic use ; Stroke/etiology ; Stroke/prevention & control
Chemical Substances	Hedgehog Proteins ; Neuroprotective Agents ; SHH protein, human ; Small Molecule Libraries
Language	English
Publishing date	2021-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-021-01408-7
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