Increased Neurogenesis and Astrogenesis from Neural Progenitor Cells Grafted in the Hippocampus of <i>GFAP</i>−/−<i>Vim</i>−/− Mice

Widestrand, Åsa; Faijerson, Jonas; Wilhelmsson, Ulrika; Smith, Peter L. P.; Li, Li-Zhen; Sihlbom, Carina; Eriksson, Peter S.; Pekny, Milos

doi:10.1634/stemcells.2007-0122

Cited by 87 publications

(72 citation statements)

References 42 publications

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“…Our results showed that all VCCs in the lateral, the anterior and the posterior horn (outside of the EZ) of the spinal cord of G93A SOD1 transgenic mice overlapped to express GFAP; thus, it is suggested that an increase in the numbers of VCCs represents astrogenesis [30] and an astrocyte regenerative response from VCCs occurred in the spinal cord of ALS disease-like transgenic (G93A SOD1) mice.…”

Section: Discussionmentioning

confidence: 99%

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

et al. 2015

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The reason for regeneration in the adult spinal cord during motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains largely unknown. To this end, we studied the alteration of vimentin (a neural precursor cells marker in CNS)-containing cells (VCCs) in spinal cord during different stages of ALS used C57BL/6J G93A SOD1 transgenic mice mimicking ALS. Results showed that VCCs were mostly distributed in the ependymal zone (EZ) surrounding the central canal of spinal cord in SOD1 wild type mice; a few of VCCs were sparsely distributed in other regions. However, the number of VCCs significantly increased in the spinal cord during the onset and progression stages of ALS. They were extensively distributed in the EZ, the anterior, the lateral and the posterior horn of grey matter, particularly in the posterior horn region at the progression stage. A majority of VCCs in the anterior, the lateral and the posterior horn of grey matter (outside of EZ) generated astrocytes, but no neurons, oligodendrocytes and microgliocytes. Our results suggested that there was a potential astrocyte regenerative response to motor neuron degeneration in motor neurons-degenerated regions in the adult spinal cord during the onset and progression stages of ALS-like disease. The regenerative responses in the adult spinal cord of ALS-like mice may be a potential pathway in attempting to repair the degenerated motor neurons and restore the dysfunctional neural circuitry.

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Section: Discussionmentioning

confidence: 99%

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

et al. 2015

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“…5K). The expression of glial markers, including GFAP and VIM (36,37), remained almost unaltered following ZMYND8 silencing (Fig. 5K).…”

Section: Journal Of Biological Chemistrymentioning

confidence: 96%

Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8

Adhikary

Sanyal

Basu

et al. 2016

Journal of Biological Chemistry

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ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a newly identified component of the transcriptional coregulator network, was found to interact with the Nucleosome Remodeling and Deacetylase (NuRD) complex. Previous reports have shown that ZMYND8 is instrumental in recruiting the NuRD complex to damaged chromatin for repressing transcription and promoting double strand break repair by homologous recombination. However, the mode of transcription regulation by ZMYND8 has remained elusive. Here, we report that through its specific key residues present in its conserved chromatin-binding modules, ZMYND8 interacts with the selective epigenetic marks H3.1K36Me2/H4K16Ac. Furthermore, ZMYND8 shows a clear preference for canonical histone H3.1 over variant H3.3. Interestingly, ZMYND8 was found to be recruited to several developmental genes, including the all-trans-retinoic acid (ATRA)-responsive ones, through its modified histone-binding ability. Being itself inducible by ATRA, this zinc finger transcription factor is involved in modulating other ATRA-inducible genes. We found that ZMYND8 interacts with transcription initiation-competent RNA polymerase II phosphorylated at Ser-5 in a DNA templatedependent manner and can alter the global gene transcription. Overall, our study identifies that ZMYND8 has CHD4-independent functions in regulating gene expression through its modified histone-binding ability.ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) is a putative chromatin reader/effector harboring a PWWP domain, a bromodomain, and a PHD type zinc finger. It associates with the CHD4 protein of NuRD chromatin remodeling complex implicated in gene transcription, cell cycle progression, and genome integrity (1, 2). Reader proteins specifically recognize histone post-translational modifications (PTMs) 5 and translate such recognition(s) into meaningful biological outcomes by virtue of either their intrinsic activities or those of their interacting partners (3). These readers may interpret histone PTMs via "monovalent" or "multivalent" recognition (4). In monovalent recognition, a chromatin reader recognizes one histone PTM. In contrast, in multivalent recognition, readers recognize multiple histone modifications intra/inter-nucleosomally. An accessible surface is provided by these readers (such as a cavity or surface groove), which accommodates the modified histone residues, and determines the modification (e.g. acetylation versus methylation) or state specificity (such as mono-versus trimethylation of lysine) (3).ZMYND8 is a well known component of the transcription coregulator complex and is associated with several demethylase machinery components, including KDM5A, KDM5C, or LSD1 (5, 6). Through its ability to interact with Xenopus RCoR2, ZMYND8 plays a significant role in embryonic neural differentiation (7). Apart from this, ZMYND8 is also involved in T-cell lymphoma and breast and cervical cancer (8 -10). Another interesting feature is that ZMYND8 is significantly involved...

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“…Thus the development of drugs that target the classical cascade may be a useful treatment for the neurodegenerative conditions. Double GFAP and vimentin knockout mice have fewer surviving astrocytes and neurons derived from a transplant of neural progenitor cells into the hippocampus (Widestrand et al, 2007). This may suggest that reactive astrocytes can prime areas of the CNS to allow the survival of neuro-precursor cells or allow the integration of these cells into astrocytes and neurons at sites of injury.…”

Section: Chronic Astrogliosismentioning

confidence: 99%

Astrocyte function and role in motor neuron disease: A future therapeutic target?

Blackburn

Sargsyan

Monk

et al. 2009

Glia

156

111

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Astrocytes are the most numerous cell type within the central nervous system (CNS) and perform a variety of tasks, from axon guidance and synaptic support, to the control of the blood brain barrier and blood flow. To perform these roles, there is a great variety of astrocytes. In this review, we summarize the function of astrocytes, in particular, their role in maintaining homeostasis at the synapse, regulating neuronal signaling, protecting neurons from oxidative damage, and determining the fate of endogenous neural precursors. The review also highlights recent developments indicating the role of astrocytes in motor neuron disease (MND), emphasizing their potential as therapeutic targets and agents in cell replacement therapy. The Cu-Zn superoxide dismutase (SOD1) gene that has been implicated in 20% of cases of familial MND must be expressed in the glial cells as well as motor neurons to produce the disease state in murine models of disease. Selectively reducing mutant SOD1 (mSOD1) in astrocytes does not affect disease onset but slows disease progression, whereas reducing mSOD1 in motor neurons delays disease onset and slows early disease but has less effect on life span. This suggests that glial cells represent potential therapeutic targets in MND. However, the lack of specific markers for astrocytes, their precursors, and sub-types means that our knowledge of astrocyte development/differentiation and response to injury lags far behind our understanding of function. Only by filling this knowledge gap can astrocytes be effectively targeted or replaced to successfully treat chronic CNS disorders such as MND.

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Increased Neurogenesis and Astrogenesis from Neural Progenitor Cells Grafted in the Hippocampus of GFAP−/−Vim−/− Mice

Abstract: ABSTRACT

Cited by 87 publications

References 42 publications

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8

Astrocyte function and role in motor neuron disease: A future therapeutic target?

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