scholarly journals Cell-Type-Specific Profiling of Gene Expression and Chromatin Binding without Cell Isolation: Assaying RNA Pol II Occupancy in Neural Stem Cells

2013 ◽  
Vol 26 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Tony D. Southall ◽  
Katrina S. Gold ◽  
Boris Egger ◽  
Catherine M. Davidson ◽  
Elizabeth E. Caygill ◽  
...  

Stem Cells ◽  
2019 ◽  
Vol 37 (9) ◽  
pp. 1223-1237 ◽  
Author(s):  
Valerio Corvaglia ◽  
Domenica Cilli ◽  
Chiara Scopa ◽  
Rossella Brandi ◽  
Ivan Arisi ◽  
...  


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Drew Neavin ◽  
Quan Nguyen ◽  
Maciej S. Daniszewski ◽  
Helena H. Liang ◽  
Han Sheng Chiu ◽  
...  

Abstract Background The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) has provided a foundation for in vitro human disease modelling, drug development and population genetics studies. Gene expression plays a critical role in complex disease risk and therapeutic response. However, while the genetic background of reprogrammed cell lines has been shown to strongly influence gene expression, the effect has not been evaluated at the level of individual cells which would provide significant resolution. By integrating single cell RNA-sequencing (scRNA-seq) and population genetics, we apply a framework in which to evaluate cell type-specific effects of genetic variation on gene expression. Results Here, we perform scRNA-seq on 64,018 fibroblasts from 79 donors and map expression quantitative trait loci (eQTLs) at the level of individual cell types. We demonstrate that the majority of eQTLs detected in fibroblasts are specific to an individual cell subtype. To address if the allelic effects on gene expression are maintained following cell reprogramming, we generate scRNA-seq data in 19,967 iPSCs from 31 reprogramed donor lines. We again identify highly cell type-specific eQTLs in iPSCs and show that the eQTLs in fibroblasts almost entirely disappear during reprogramming. Conclusions This work provides an atlas of how genetic variation influences gene expression across cell subtypes and provides evidence for patterns of genetic architecture that lead to cell type-specific eQTL effects.



2021 ◽  
Author(s):  
yuanyuan wang ◽  
mingyan lin

The pathology underlying schizophrenia (SCZ) involves cell type-specific and developmental stage-specific dysregulation of multiple gene regulatory networks dominated by some key transcription factors, such as SCZ risk gene transcription factor 4 (TCF4). Previous studies on the regulatory mechanism of TCF4 use SY5Y as the cellular model, which could not reflect its cell type-specific role in the real world. Using the transcriptional profile of whole brain during development stages and single-cell transcriptome data in the developing human prefrontal cortex, we found that TCF4 was preferentially expressed in the interneuron. Chromatin immunoprecipitation combined with sequencing (ChIP-Seq) in human embryonic stem cells (hESC)-derived interneurons revealed that TCF4 primarily activate transcription of genes associated with cortex development and telencephalon regionalization in a long-range manner. As expected, the downstream targets of TCF4 were distinct in inhibitory neurons and neural stem cells during early neurodevelopment, justifying the importance of our study. Deeper investigation further revealed that TCF4 regulate genes related to neurotransmission distally in interneuron in a c-FOS dependent manner, while TCF4 and TCF3 synergistically regulate genes associated with cell proliferation associated proximally in neural stem cells. Our findings suggested that defects in development of interneuron, for instance as a result of TCF4 abnormality, may break excitation and inhibition balance and contribute significantly to the risk of SCZ.



2014 ◽  
Vol 45 ◽  
pp. 192-200 ◽  
Author(s):  
Nasir Malik ◽  
Anastasia G. Efthymiou ◽  
Karly Mather ◽  
Nathaniel Chester ◽  
Xiantao Wang ◽  
...  


PLoS Genetics ◽  
2020 ◽  
Vol 16 (4) ◽  
pp. e1008661 ◽  
Author(s):  
Hasthi Ram ◽  
Sudeep Sahadevan ◽  
Nittaya Gale ◽  
Monica Pia Caggiano ◽  
Xiulian Yu ◽  
...  


Author(s):  
Tamaki Ishima ◽  
Sebastian Illes ◽  
Yoshimi Iwayama ◽  
Brian Dean ◽  
Takeo Yoshikawa ◽  
...  


2013 ◽  
Vol 28 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Marica Gemei ◽  
Rosa Di Noto ◽  
Peppino Mirabelli ◽  
Luigi Del Vecchio

In colorectal cancer, CD133+ cells from fresh biopsies proved to be more tumorigenic than their CD133– counterparts. Nevertheless, the function of CD133 protein in tumorigenic cells seems only marginal. Moreover, CD133 expression alone is insufficient to isolate true cancer stem cells, since only 1 out of 262 CD133+ cells actually displays stem-cell capacity. Thus, new markers for colorectal cancer stem cells are needed. Here, we show the extensive characterization of CD133+ cells in 5 different colon carcinoma continuous cell lines (HT29, HCT116, Caco2, GEO and LS174T), each representing a different maturation level of colorectal cancer cells. Markers associated with stemness, tumorigenesis and metastatic potential were selected. We identified 6 molecules consistently present on CD133+ cells: CD9, CD29, CD49b, CD59, CD151, and CD326. By contrast, CD24, CD26, CD54, CD66c, CD81, CD90, CD99, CD112, CD164, CD166, and CD200 showed a discontinuous behavior, which led us to identify cell type-specific surface antigen mosaics. Finally, some antigens, e.g. CD227, indicated the possibility of classifying the CD133+ cells into 2 subsets likely exhibiting specific features. This study reports, for the first time, an extended characterization of the CD133+ cells in colon carcinoma cell lines and provides a “dictionary” of antigens to be used in colorectal cancer research.



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