Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina

Dvoriantchikova, Galina; Perea-Martinez, Isabel; Pappas, Steve; Barry, Ariel Faye; Danek, Dagmara; Dvoriantchikova, Xenia; Pelaez, Daniel; Ivanov, Dmitry

doi:10.1371/journal.pone.0131054

Cited by 17 publications

(24 citation statements)

References 41 publications

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“…Given the NOTCH pathway's essential role in preventing progenitor differentiation in the mammary gland (and many other tissues types), we suggest that the canonical NOTCH ligands Jag1/Jag2 and the noncanonical Dlk1 may activate Notch1/Notch3/Rbpj, preventing differentiation of all lacrimal gland cells expressing NOTCH receptors. 23 , 28 – 32 Meanwhile, because Elf5 mediates mammary gland progenitor cell differentiation by inhibiting NOTCH signaling, we can suggest that a similar process may occur during lacrimal gland development, as Elf5 expression—while present in the embryonic gland—was significantly upregulated in the adult lacrimal gland. 33 …”

Section: Discussionmentioning

confidence: 89%

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Molecular Profiling of the Developing Lacrimal Gland Reveals Putative Role of Notch Signaling in Branching Morphogenesis

Dvoriantchikova

Tao

Pappas

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeAlthough normal function of the lacrimal gland is essential for vision (and thus for human well-being), the lacrimal gland remains rather poorly understood at a molecular level. The purpose of this study was to identify new genes and signaling cascades involved in lacrimal gland development.MethodsTo identify these genes, we used microarray analysis to compare the gene expression profiles of developing (embryonic) and adult lacrimal glands. Differential data were validated by quantitative RT-PCR, and several corresponding proteins were confirmed by immunohistochemistry and Western blot analysis. To evaluate the role of NOTCH signaling in lacrimal gland (LG) development, we used the NOTCH inhibitor DAPT and conditional Notch1 knockouts.ResultsOur microarray data and an in silico reconstruction of cellular networks revealed significant changes in the expression patterns of genes from the NOTCH, WNT, TGFβ, and Hedgehog pathways, all of which are involved in the regulation of epithelial-to-mesenchymal transition (EMT). Our study also revealed new putative lacrimal gland stem cell/progenitor markers. We found that inhibiting Notch signaling both increases the average number of lacrimal gland lobules and reduces the size of each lobule.ConclusionsOur findings suggest that NOTCH-, WNT-, TGFβ-, and Hedgehog-regulated EMT transition are critical mechanisms in lacrimal gland development and morphogenesis. Our data also supports the hypothesis that NOTCH signaling regulates branching morphogenesis in the developing lacrimal gland by suppressing cleft formation.

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Section: Discussionmentioning

confidence: 89%

“…Quantitative RT-PCR analysis was performed as described previously 22 , 23 using gene-specific primers ( Table 1 ). Relative expression was calculated by comparison with a standard curve following normalization to expression of the housekeeping gene β-actin (Actb), chosen as a control.…”

Section: Methodsmentioning

confidence: 99%

Molecular Profiling of the Developing Lacrimal Gland Reveals Putative Role of Notch Signaling in Branching Morphogenesis

Dvoriantchikova

Tao

Pappas

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Quantitative RT-PCR analysis was performed as described previously using gene-specific primers (Supplementary Data S10) 55,56 . Briefly, RNA samples were extracted from adult RPE cells using the Absolutely RNA® Nanoprep kit (Agilent Technologies, Santa Clara, CA) and reverse transcribed with SuperScript III Reverse Transcriptase (ThermoFisher Scientific, Grand Island, NY) to synthesize cDNA.…”

Section: Methodsmentioning

confidence: 99%

The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue

Dvoriantchikova

Seemungal

Ivanov

2019

Sci Rep

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The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal tissue. RPE were analyzed using microarray, ChIP-seq, and whole-genome bisulfite sequencing approaches. We found that the majority of key genes required for progenitor phenotypes were in a permissive chromatin state and unmethylated in RPE. We observed that the majority of non-photoreceptor genes had promoters in a repressive chromatin state, but these promoters were in unmethylated or low-methylated regions. Meanwhile, the majority of promoters for photoreceptor genes were found in a permissive chromatin state, but were highly-methylated. Methylome states of photoreceptor-related genes in adult RPE and embryonic retina (which mostly contain progenitors) were very similar. However, promoters of these genes were demethylated and activated during retinal development. Our data suggest that, epigenetically, adult murine RPE cells are a progenitor-like cell type. Most likely two mechanisms prevent adult RPE from reprogramming and differentiating into retinal neurons: 1) repressive chromatin in the promoter regions of non-photoreceptor retinal neuron genes; 2) highly-methylated promoters of photoreceptor-related genes.

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“…More importantly, PTPRZ1 interaction with MDK promotes neuron migration [50]. SVZ expressed high levels of NOTCH3 interacting with receptor DLL3 on deeper layer cells and upper layer cells, which could modulate cellular differentiation, fates for terminal neuronal differentiation and links to progression toward a neuronal fate in the developing cortex [51, 52](Fig. 4E).…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptomic analysis identifies neocortical developmental differences between human and mouse

Zhou

Wang

Zhang

et al. 2020

Preprint

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20Background: The specification and differentiation of neocortical projection neurons is a 21complex process under precise molecular regulation; however, little is known about the 22 similarities and differences in cerebral cortex development between human and mouse at 23 single-cell resolution. 24Results: Here, using single-cell RNA-seq (scRNA-seq) data we explore the divergence 25 and conservation of human and mouse cerebral cortex development using 18,446 and 26 7,610 neocortical cells. Systematic cross-species comparison reveals that the overall 27 transcriptome profile in human cerebral cortex is similar to that in mouse such as cell types 28 and their markers genes. By single-cell trajectories analysis we find human and mouse 29 excitatory neurons have different developmental trajectories of neocortical projection 30 neurons, ligand-receptor interactions and gene expression patterns. Further analysis 31 reveals a refinement of neuron differentiation that occurred in human but not in mouse, 32suggesting that excitatory neurons in human undergo refined transcriptional states in later 33 development stage. By contrast, for glial cells and inhibitory neurons we detected 34 conserved developmental trajectories in human and mouse. 35 Conclusions: Taken together, our study integrates scRNA-seq data of cerebral cortex 36 development in human and mouse, and uncovers distinct developing models in 37 neocortical projection neurons. The earlier activation of cognition -related genes in human 38 may explain the differences in behavior, learning or memory abilities between the two 39 species. 40 41 Cognition 44 45 46 3 Background 47The mammalian cerebral cortex develops via a complex process of cell proliferation, 48 differentiation, and migration events. The molecular features of the human brain at 49 gestational weeks 7-23 are similar to those of the mouse at postnatal days 14.5 to birth 50 (P0) and reveal gene expression differences between the two species [1, 2]. Interneurons 51 and projection neurons, which are the two major classes of neurons, populate the 52 neocortex. Interneurons show largely GABAergic, connecting locally within the neocortex, 53 and are generated by progenitors in the ventral telencephalic (inhibitory cortical 54 interneuron producing) radial glia, before migrating from sub pallial ganglionic eminences 55 into the cortex [3][4][5][6]. By contrast, projection neurons are excitatory, which are generated 56 by progenitors in the dorsal telencephalic (excitatory cortical neuron producing) radial glia 57 [7][8][9]. 58 59Despite immense efforts over the past decades to study the cell types, function, 60 differentiation for the mammalian cerebral cortex, especially human and mouse, large 61 differences and conservation are observed in human versus animal models [10][11][12]. 62Elucidating the conserved, divergent and cellular architecture of developing the cerebral 63 cortex, especially projection neurons developments, may highlight to understanding 64 susceptibility to neurological diseases and the o...

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Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina

Cited by 17 publications

References 41 publications

Molecular Profiling of the Developing Lacrimal Gland Reveals Putative Role of Notch Signaling in Branching Morphogenesis

Molecular Profiling of the Developing Lacrimal Gland Reveals Putative Role of Notch Signaling in Branching Morphogenesis

The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue

Single-cell transcriptomic analysis identifies neocortical developmental differences between human and mouse

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