Mouse neural progenitor cells differentiate into oligodendrocytes in the brain of a knockout mouse model of Canavan disease

2004 ◽  
Vol 153 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Sankar Surendran ◽  
Lamya S. Shihabuddin ◽  
Jennifer Clarke ◽  
Tatyana V. Taksir ◽  
Gregory R. Stewart ◽  
...  
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Knockout Mouse ◽  
Neural Progenitor Cells ◽  
Canavan Disease ◽  
Neural Progenitor ◽  
Knockout Mouse Model ◽  
The Brain

scholarly journals Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon

2018 ◽  
Vol 43 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Kanako Saito ◽  
Ryotaro Kawasoe ◽  
Hiroshi Sasaki ◽  
Ayano Kawaguchi ◽  
Takaki Miyata
Keyword(s):  
Progenitor Cells ◽  
Neural Tube ◽  
Neural Progenitor Cells ◽  
Three Dimensional ◽  
Neural Progenitor ◽  
Hippo Signaling ◽  
Apical Surface ◽  
Elevated Expression ◽  
Underlying Mechanisms ◽  
The Brain

Abstract Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.

scholarly journals Retinal transplantation of neural progenitor cells derived from the brain of GFP transgenic mice

2003 ◽  
Vol 43 (16) ◽  
pp. 1699-1708 ◽  
Author(s):  
Hiroyuki Mizumoto ◽  
Keiko Mizumoto ◽  
Marie A Shatos ◽  
Henry Klassen ◽  
Michael J Young
Keyword(s):  
Transgenic Mice ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Retinal Transplantation ◽  
The Brain

scholarly journals Transcriptional Heterogeneity Governs Cell Fate Diversification during Pre-Leukemia to Leukemia Progression

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Shikha Gupta ◽  
Ana Filipa Domingues ◽  
Oliwia Cyran ◽  
George Giotopoulos ◽  
Sudhakaran Prabakaran ◽  
...  
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Knockout Mouse ◽  
Conditional Knockout ◽  
Ribosomal Biogenesis ◽  
Cell Fates ◽  
Knockout Mouse Model ◽  
Recurrent Mutations

Acute myeloid leukemia (AML) is a heterogenous clonal disorder of hematopoietic progenitor cells with a dismal survival. It has a strong reliance on epigenetic and transcriptional factors for disease progression. Accordingly, we have previously identified KAT2A, a histone acetyl-transferase, as a requirement for AML maintenance; where chemical inhibition of KAT2A promotes differentiation of AML cell lines (Tzelepis et al., 2016, Cell Reports 17, 1193-1205). More recently, using a conditional knockout mouse model for Kat2a we showed that it sustains KMT2A/MLLT3 AML stem cells. Kat2a is a classical regulator of transcriptional variability, it's loss leads to cell-to-cell heterogeneity in transcription levels specifically from genes involved in ribosomal biogenesis and translation (Domingues et al., 2020, eLife 9:e51754). No recurrent mutations in the KAT2A gene have been described in AML, and it is unclear if and how it participates in pre-leukemia-to-AML progression. Herein, we use our conditional Kat2a knockout mouse model to analyze the effects of Kat2a loss in biology of RUNX1-RUNX1T1(9a) and Idh1R132H-initiated AML. These models represent forms of human disease with a prolonged pre-leukemia phase that typically require additional mutations for leukemia progression. We observed that loss of Kat2a accelerates leukemia initiation and progression in vivo. This acceleration was a consequence of fixation of transformed Kat2a KO cells in vivo which reflects as enhanced self-renewal capacity in vitro as measured by serial re-plating colony forming assay. Given the central role of Kat2a in limiting cell-to-cell transcription heterogeneity, we interrogated a potential link between loss of Kat2a, its consequent increase in transcriptional heterogeneity and pre-leukemia progression. For this, we performed single-cell RNA sequencing (scRNA-seq) of early-stage Kat2a WT and Kat2a KO RUNX1-RUNX1T1(9a) pre-leukaemia. Compatible with our previous observation, we observed that Kat2a KO cells were more heterogenous transcriptionally. Interestingly, this was accompanied by diversification of cell fates towards B-lymphocytes and monocytes. Furthermore, pseudo-temporal ordering of single Kat2a KO cells revealed highly branched trajectory heavily populated with intermediate stages of transformation; including accumulation of leukemia progenitors with RUNX1-RUNX1T1 signature. In contrast, Kat2a WT cells have linear normal hematopoiesis trajectory with minimal branching and an abrupt transition towards candidate leukemia progenitor state. Pathway analysis of Kat2a KO leukemia progenitor cells indicated perturbation of ribosomal biogenesis and translation associated genes. In order to test how these changes contributed to transformation, we performed S6K1 inhibition on Kat2a WT cells which transiently promoted transformation in vitro in both RUNX1-RUNX1T1(9a) and Idh1R132H cells, thus, phenocopying the effects of Kat2a loss. This suggested a mechanistic contribution of observed transcriptional changes in protein synthesis machinery towards leukemia progression. Taken together, our work suggests that loss of Kat2a results in diversification of cell fates, including with increased accessibility to cell states prone to transformation. Furthermore, these cells, prone to transformation, may benefit from a low biosynthetic activity that promotes their progression to leukemia state. We hypothesize that Kat2a loss may function similarly in the context of other malignancies. In the future, this knowledge may aid in development of early diagnostic tools and suggest bespoke therapeutic interventions. Figure Disclosures Prabakaran: Noncodomics: Consultancy. Vassiliou:Kymab Ltd - Monoclonal antibody company. Currently not working in myeloid cancers or clonal haematopoiesis.: Consultancy.

Migration and Differentiation of Fetal Neural Progenitor Cells in the Brain of Ischemic Animals

2010 ◽  
Vol 1 (1) ◽  
pp. 25-34 ◽  
Author(s):  
O. M. Tsupykov ◽  
T. A. Pivneva ◽  
A. O. Poddubna ◽  
V. M. Kyryk ◽  
O. V. Kuchuk ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
The Brain

Transplantation of neural progenitor cells stimulates endogenous neurogenesis in mice after ischemic stroke

2014 ◽  
Vol 2 (1) ◽  
pp. 85-89 ◽  
Author(s):  
O. Tsupykov ◽  
V. Kyryk ◽  
A. Mamchur ◽  
P. Poberezhnyi ◽  
G. Butenko ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Brain Slices ◽  
Neural Progenitor ◽  
Short Term ◽  
Hippocampal Ca1 ◽  
Ca1 Area ◽  
Adaptation Processes ◽  
The Brain

The researchers have currently been actively investigating the possibilities for transplantation of the stem cells of various sources for treatment of the ischemic and degenerative diseases of the nervous systemInfluence of transplantation of the hippocampal neural progenitor cells (NPCs) on endogenous neurogenesis in the mice after brain ischemia-reperfusion induced by 20 min occlusion of both carotid arteries has been studied. Following 24 hours after occlusion the NPCsisolated from the hippocampus of the FVB-Cg-Tg(GFPU)5Nagy/J mice transgenic by the GFP gene were transplanted stereotactically into hippocampal CA1 area of the experimental animals. For evaluating neurogenesis in the hippocampus of the ischemic animals we used immunohistochemical staining of the brain slices for BrdU and doublecortin (DCX). It has been found that transplantation of neural progenitor cells increased the number of BrdU- and DCX-positive cells in the dentate gyrus of the hippocampus after short-term global ischemia.These data allow admit that NPC transplantation to the ischemic animals influences on endogenous adaptation processes in the brain and on the neurogenesis, in particular.

scholarly journals Abnormal development of NG2+PDGFR-α+ neural progenitor cells leads to neonatal hydrocephalus in a ciliopathy mouse model

2012 ◽  
Vol 18 (12) ◽  
pp. 1797-1804 ◽  
Author(s):  
Calvin S Carter ◽  
Timothy W Vogel ◽  
Qihong Zhang ◽  
Seongjin Seo ◽  
Ruth E Swiderski ◽  
...  
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Abnormal Development

scholarly journals Neuropathogenesis of a mouse-adapted porcine epidemic diarrhea virus infection in suckling mice

2013 ◽  
Vol 94 (4) ◽  
pp. 831-836 ◽  
Author(s):  
Osamu Kotani ◽  
Kazuya Shirato ◽  
Noriyo Nagata ◽  
Hidetoshi Ikeda ◽  
Kimimasa Takahashi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Porcine Epidemic Diarrhea Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Wide Area ◽  
Target Cells ◽  
Diarrhea Virus ◽  
Suckling Mice ◽  
Porcine Epidemic Diarrhea ◽  
The Brain

A mouse-adapted porcine epidemic diarrhea virus, MK-p10, showed higher neurovirulence in suckling mice than a non-adapted MK strain. There was no difference in virus growth, whereas clear differences between these two virus infections existed in the type of target cells infected, the spread of virus and the cytokine levels produced in the brain. In the early phase of infection, neurons, astrocytes and neural progenitor cells were infected by MK-p10, whereas neural progenitor cells were the only target cells infected by MK. On days 4–5 post-inoculation, MK-p10 antigens were distributed in a number of neurons in a wide area of the brain; however, antigens were restricted in MK infection. In moribund mice in both infection groups, viral antigens were found in a wide area of the brain. The wide spectrum of initial target cells following MK-p10 infection, as well as its faster spread in the brain, may be evidence of enhanced virulence in suckling mice.

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