scholarly journals Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Hideyuki Komori ◽  
Qi Xiao ◽  
Derek H Janssens ◽  
Yali Dou ◽  
Cheng-Yu Lee
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Functional Identity ◽  
Functional Heterogeneity ◽  
Larval Brain ◽  
Mutant Type ◽  
Differentiated Cells

The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. In this study, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.

scholarly journals Continual inactivation of genes involved in stem cell functional identity stabilizes progenitor commitment

2020 ◽  
Author(s):  
Noemi Rives-Quinto ◽  
Hideyuki Komori ◽  
Derek H. Janssens ◽  
Shu Kondo ◽  
Qi Dai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Histone Deacetylation ◽  
Type Ii ◽  
Functional Identity ◽  
Larval Brain ◽  
Intermediate Progenitors ◽  
Differentiated Cells ◽  
Mechanistic Investigation

SummaryExpansion of the pool of stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, mechanistic investigation of the competency of stem cells to generate intermediate progenitors remains impossible. Fly larval brain neuroblasts provide excellent in vivo models for investigating the regulation of stem cell functionality during neurogenesis. Type II neuroblasts undergo indirect neurogenesis by dividing asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as the master regulator that maintains type II neuroblast functional identity, including the competency to generate INPs. Successive inactivation during INP commitment inhibits tll activation by Notch, preventing INPs from reacquiring neuroblast functionality. We propose that the continual inactivation of neural stem cell functional identity genes by histone deacetylation allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.

scholarly journals Prolyl 4-hydroxylase Isoenzymes I and II Have Different Expression Patterns in Several Human Tissues

2001 ◽  
Vol 49 (9) ◽  
pp. 1143-1153 ◽  
Author(s):  
Ritva Nissi ◽  
Helena Autio–Harmainen ◽  
Pia Marttila ◽  
Raija Sormunen ◽  
Kari I. Kivirikko
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Collecting Duct ◽  
Expression Patterns ◽  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Main Form ◽  
Differentiated Cells ◽  
Capillary Endothelial Cells

Prolyl 4-hydroxylase plays a central role in the synthesis of all collagens. We have previously reported that the recently identified Type II isoenzyme is its main form in chondrocytes and possibly in capillary endothelial cells, while Type I is the main form in many other cell types. We report here that the Type II isoenzyme is clearly the main form in capillary endothelial cells and also in cultured umbilical vein endothelial cells, whereas no Type I isoenzyme could be detected in these cells by immunostaining or Western blotting. The Type II isoenzyme was also the main form in cells of the developing glomeruli in the fetal kidney and tubular structures of collecting duct caliber in both fetal and adult kidney, in occasional sinusoidal structures and epithelia of the bile ducts in the liver, and in some cells of the decidual membrane that probably represented invasive cytotrophoblasts in the placenta. Osteoblasts in a fetal calvaria, i.e., a bone developing by intramembranous ossification, stained strongly for both types of isoenzyme. The Type I isoenzyme was the main form in undifferentiated interstitial mesenchymal cells of the developing kidney, for example, and in fibroblasts and fibroblastic cells in many tissues. Skeletal myocytes and smooth muscle cells appeared to have the Type I isoenzyme as their only prolyl 4-hydroxylase form. Hepatocytes expressed small amounts of the Type I enzyme and very little if any Type II, the Type I expression being increased in malignant hepatocytes and cultured hepatoblastoma cells. The data suggest that the Type I isoenzyme is expressed especially by cells of mesenchymal origin and in developing and malignant tissues, whereas the Type II isoenzyme is expressed, in addition to chondrocytes and osteoblasts, by more differentiated cells, such as endothelial cells and cells of epithelial structures. (J Histochem Cytochem 49:1143–1153, 2001)

scholarly journals Neural Stem Cells: What Happens When They Go Viral?

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1468
Author(s):  
Yashika S. Kamte ◽  
Manisha N. Chandwani ◽  
Alexa C. Michaels ◽  
Lauren A. O’Donnell
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Cell Types ◽  
Developmental Abnormalities ◽  
Multipotent Progenitor Cells ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

scholarly journals Integrated Patterning Programs During Drosophila Development Generate the Diversity of Neurons and Control Their Mature Properties

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Anthony M. Rossi ◽  
Shadi Jafari ◽  
Claude Desplan
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Temporal Patterning ◽  
Long Time ◽  
Neuronal Types ◽  
And Control

During the approximately 5 days of Drosophila neurogenesis (late embryogenesis to the beginning of pupation), a limited number of neural stem cells produce approximately 200,000 neurons comprising hundreds of cell types. To build a functional nervous system, neuronal types need to be produced in the proper places, appropriate numbers, and correct times. We discuss how neural stem cells (neuroblasts) obtain so-called area codes for their positions in the nervous system (spatial patterning) and how they keep time to sequentially produce neurons with unique fates (temporal patterning). We focus on specific examples that demonstrate how a relatively simple patterning system (Notch) can be used reiteratively to generate different neuronal types. We also speculate on how different modes of temporal patterning that operate over short versus long time periods might be linked. We end by discussing how specification programs are integrated and lead to the terminal features of different neuronal types. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

Differentiated Cells Derived from Fetal Neural Stem Cells Improve Motor Deficits in a Rat Model of Parkinson's Disease

2015 ◽  
Vol 1 (2) ◽  
pp. 75-85 ◽  
Author(s):  
Wei Wang ◽  
Hao Song ◽  
Aifang Shen ◽  
Chao Chen ◽  
Yanming Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Neural Stem Cells ◽  
Rat Model ◽  
Motor Deficits ◽  
Differentiated Cells

417. In vivo and in vitro evidence for cancer stem cells in human endometrial cancer

2008 ◽  
Vol 20 (9) ◽  
pp. 97
Author(s):  
S. Hubbard ◽  
C. E. Gargett
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Single Cell ◽  
Type I ◽  
Type Ii ◽  
Cloning Efficiency ◽  
Isolated Cells ◽  
Vimentin Expression ◽  
Self Renewal

Cancer stem cells (CSCs) have been identified in solid human cancers, including breast, colon, and ovary. Recent evidence suggests that the highly regenerative human endometrium harbors rare populations of epithelial stem/progenitor cells1. We hypothesised that CSCs are responsible for the epithelial neoplasia associated with endometrial carcinoma (EC), the most common gynaecological malignancy in women. The aim of this study was to demonstrate that a rare population of EC cells posses CSC properties. Stem cell characteristics were assessed in 25 EC and 2 endometrial hyperplasia tissues obtained from women aged 62 ± 9 yrs. Samples were cultured at clonal densities (100–500 cells/cm2) for 3–5 wks to determine cloning efficiency. Individual clones were serially subcloned (<10 cells/cm2) every 2–4 wks to determine self renewal capacity. Isolated cells in serial dilution (103–106 cells) were placed under the kidney capsule of immunocompromised mice for 12–16 wks to examine for the presence of tumour initiating cells (TIC). Resulting tumours and original parent tumours were examined for markers by immunohistochemistry. Most samples (23/26) contained rare colony forming cells. The cloning efficiency was 0.23% ± 0.28% (n = 11) in G1, 0.78% ± 0.67% (n = 8) in G2, 0.22% ± 0.21% (n = 3) in G3, 0.03% (n = 2) in type II tumours, and 0.14% (n = 2) in hyperplasia samples, and did not differ significantly between grades or between type I EC and normal endometrial epithelial samples 1. Single cell derived clones subcloned 2.5 ± 1.4 (n = 11), 3.2 ± 0.4 (n = 5), 3.5 (n = 2), 3.0 ± 1.7 (n = 3), and 2.5 (n = 2) times in G1, G2, G3, type II tumours and hyperplasia samples respectively, indicating increasing self renewal capacity with increasing tumour grade. Transplanted EC single cell suspensions initiated tumour growth with similar morphology, ERα, PR, EpCAM, cytokeratin, and vimentin expression as the parent tumour, indicating the presence of TIC. This evidence suggests that rare cells possessing the CSC properties of clonogenicty, self renewal, and tumorigenicity, may be responsible for the initiation and progression of EC. (1) Chan RWS et al. (2004). Biology of Reproduction. 70:1738–1750

scholarly journals Posttranslational regulation of keratins: degradation of mouse and human keratins 18 and 8.

1989 ◽  
Vol 9 (4) ◽  
pp. 1553-1565 ◽  
Author(s):  
D A Kulesh ◽  
G Ceceña ◽  
Y M Darmon ◽  
M Vasseur ◽  
R G Oshima
Keyword(s):  
Cell Types ◽  
Immunofluorescent Staining ◽  
Type I ◽  
Type Ii ◽  
Tail Domain ◽  
Proteolytic System ◽  
L Cells ◽  
Adult Mice ◽  
3T3 Fibroblasts ◽  
Keratin Filament

Human keratin 18 (K18) and keratin 8 (K8) and their mouse homologs, Endo B and Endo A, respectively, are expressed in adult mice primarily in a variety of simple epithelial cell types in which they are normally found in equal amounts within the intermediate filament cytoskeleton. Expression of K18 alone in mouse L cells or NIH 3T3 fibroblasts from either the gene or a cDNA expression vector results in K18 protein which is degraded relatively rapidly without the formation of filaments. A K8 cDNA containing all coding sequences was isolated and expressed in mouse fibroblasts either singly or in combination with K18. Immunoprecipitation of stably transfected L cells revealed that when K8 was expressed alone, it was degraded in a fashion similar to that seen previously for K18. However, expression of K8 in fibroblasts that also expressed K18 resulted in stabilization of both K18 and K8. Immunofluorescent staining revealed typical keratin filament organization in such cells. Thus, expression of a type I and a type II keratin was found to be both necessary and sufficient for formation of keratin filaments within fibroblasts. To determine whether a similar proteolytic system responsible for the degradation of K18 in fibroblasts also exists in simple epithelial cells which normally express a type I and a type II keratin, a mutant, truncated K18 protein missing the carboxy-terminal tail domain and a conserved region of the central, alpha-helical rod domain was expressed in mouse parietal endodermal cells. This resulted in destabilization of endogenous Endo A and Endo B and inhibition of the formation of typical keratin filament structures. Therefore, cells that normally express keratins contain a proteolytic system similar to that found in experimentally manipulated fibroblasts which degrades keratin proteins not found in their normal polymerized state.

Characterizing the effect of substrate stiffness on neural stem cell differentiation

2012 ◽  
Vol 1498 ◽  
pp. 47-52
Author(s):  
Colleen T. Curley ◽  
Kristen Fanale ◽  
Sabrina S. Jedlicka
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Neural Stem Cells ◽  
Cortical Neurons ◽  
Type I Collagen ◽  
Stem Cell Differentiation ◽  
Synaptic Proteins ◽  
Substrate Stiffness ◽  
Type I ◽  
Polyacrylamide Gels

ABSTRACTDifferentiated neurons (dorsal root ganglia and cortical neurons) have been shown to develop longer neurite extensions on softer materials than stiffer ones, but previous studies do not address the ability of neural stem cells to undergo differentiation as a result of material elasticity. In this study, we investigate neuronal differentiation of C17.2 neural stem cells due to growth on polyacrylamide gels of variable elastic moduli. Neurite growth, synapse formation, and mode of division (asymmetric vs. symmetric) were all assessed to characterize differentiation. C17.2 neural stem cells were seeded onto polyacrylamide gels coated with Type I collagen. The cells were then serum starved over a 14 day period, fixed, and analyzed for biochemical markers of differentiation. For division studies, time-lapse imaging of cells on various substrates was performed during serum withdrawal using the Nikon Biostation. Division events were analyzed using ImageJ to quantify sizes of resulting daughter. Data shows that C17.2 cell differentiation (as dictated by number and type of division events) is dependent upon substrate stiffness, with softer polyacrylamide surfaces (140 Pa) leading to increased populations of neurons and increased neurite length. Our data also indicates that the ability of neural stem cells to express synaptic proteins and develop synapses is dependent upon material elasticity.

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