The Transcription Factor NFIA Controls the Onset of Gliogenesis in the Developing Spinal Cord

Deneen, Benjamin; Ho, Ritchie; Lukaszewicz, Agnès; Hochstim, Christian; Gronostajski, Richard M.; Anderson, David J.

doi:10.1016/j.neuron.2006.11.019

Cited by 449 publications

(567 citation statements)

References 75 publications

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“…At D24, pTEL progenitor clusters expressed slightly higher levels of MKI67 and GPC3, indicating these early populations are mitotically active (Filmus, 2001;Scholzen and Gerdes, 2000). By D54 and D100, pTEL progenitor clusters express NFIA and HOPX, consistent with a transition to astrogliogenesis and/or outer radial glial cell production (Deneen et al, 2006;Pollen et al, 2015;Shu et al, 2003;Thomsen et al, 2016). After D54, pMGE clusters also express higher levels of HOPX, in addition to AQP4, S100B, ANXA1, and S100A10 compared to earlier clusters.…”

Section: Scrna-seq Analysis Of In Vitro-derived Human Interneuronsmentioning

confidence: 85%

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Close¹,

Yao²,

Miller³

et al. 2017

Neuron

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SummaryGABAergic interneurons are essential for neural circuit function and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and ultimately therapeutic cell replacement. We describe here a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation timecourse of cell types using single-cell RNAseq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late. By comparing the transcriptomes of immature interneurons to more mature neurons, we identified genes important for human interneuron differentiation. Many of these genes were previously implicated in neurodevelopmental and neuropsychiatric disorders. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access

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Section: Scrna-seq Analysis Of In Vitro-derived Human Interneuronsmentioning

confidence: 85%

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Close¹,

Yao²,

Miller³

et al. 2017

Neuron

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“…By immunostaining and morphology, both PSC-NPCs and 16-week-tissue-derived NPCs had the capacity to generate both Tuj1+ neurons and GFAP+ glia ( Figure 1A′); however, the p1 PSC-NPCs mostly generated neurons (Tuj1+), while the 16-week-old-tissue-derived NPCs mostly produced glia (GFAP+) ( Figure 1A″). Because neurogenesis precedes gliogenesis during in vivo development [26], these data suggest that PSC-NPCs may represent earlier developmental time points than the NPCs derived from 16-week-old fetal tissue. …”

Section: Generation Of Ectodermmentioning

confidence: 86%

Defining the nature of human pluripotent stem cell progeny

et al. 2011

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While it is clear that human pluripotent stem cells (hPSCs) can differentiate to generate a panoply of various cell types, it is unknown how closely in vitro development mirrors that which occurs in vivo. To determine whether human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) make equivalent progeny, and whether either makes cells that are analogous to tissue-derived cells, we performed comprehensive transcriptome profiling of purified PSC derivatives and their tissue-derived counterparts. Expression profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for the neural, hepatic, and mesenchymal lineages, and an absence of re-expression from exogenous reprogramming factors in hiPSC progeny. However, when compared to a tissuederived counterpart, the progeny of both hESCs and hiPSCs maintained expression of a subset of genes normally associated with early mammalian development, regardless of the type of cell generated. While pluripotent genes (OCT4, SOX2, REX1, and NANOG) appeared to be silenced immediately upon differentiation from hPSCs, genes normally unique to early embryos (LIN28A, LIN28B, DPPA4, and others) were not fully silenced in hPSC derivatives. These data and evidence from expression patterns in early human fetal tissue (3-16 weeks of development) suggest that the differentiated progeny of hPSCs are reflective of very early human development (< 6 weeks). These findings provide support for the idea that hPSCs can serve as useful in vitro models of early human development, but also raise important issues for disease modeling and the clinical application of hPSC derivatives.

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“…Sox9 is initially (E8.5–E18.5) expressed in all glial (precursor) cells, and is subsequently downregulated in myelinating oligodendrocytes (Stolt et al, 2003) and becomes astrocyte‐specific (Sun et al, 2017). Also NFIA is initially (E11.5) expressed in all developing glial cells, but downregulates Olig2 and becomes exclusive to astrocytes at E13.5–E16.5 (Deneen et al, 2006; Molofsky et al, 2012). In the developing neural tube of rats, neural stem cell marker nestin is expressed directly after closing of the neural tube at E11 (Lendahl, Zimmerman, & McKay, 1990), whereas GFAP expression starts later at E18 (Oudega & Marani, 1991).…”

Section: Discussionmentioning

confidence: 99%

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Leferink

Breeuwsma

Bugiani

et al. 2017

Glia

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Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post‐mortem tissue of two VWM patients, a 13‐year‐old boy and a 6‐year‐old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

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The Transcription Factor NFIA Controls the Onset of Gliogenesis in the Developing Spinal Cord

Cited by 449 publications

References 75 publications

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Defining the nature of human pluripotent stem cell progeny

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

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