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Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages

Overview of attention for article published in Stem Cell Research & Therapy, May 2018
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Title
Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages
Published in
Stem Cell Research & Therapy, May 2018
DOI 10.1186/s13287-018-0848-7
Pubmed ID
Authors

Jen-Hua Chuang, Aliaksandr A. Yarmishyn, De-Kuang Hwang, Chih-Chien Hsu, Mong-Lien Wang, Yi-Ping Yang, Ke-Hung Chien, Shih-Hwa Chiou, Chi-Hsien Peng, Shih-Jen Chen

Abstract

Differentiation of human induced pluripotent stem cells (hiPSCs) into retinal lineages offers great potential for medical application. Therefore, it is of crucial importance to know the key intrinsic regulators of differentiation and the specific biomarker signatures of cell lineages. In this study, we used microarrays to analyze transcriptomes of terminally differentiated retinal ganglion cell (RGC) and retinal pigment epithelium (RPE) lineages, as well as intermediate retinal progenitor cells of optic vesicles (OVs) derived from hiPSCs. In our analysis, we specifically focused on the classes of transcripts that encode intrinsic regulators of gene expression: the transcription factors (TFs) and epigenetic chromatin state regulators. We applied two criteria for the selection of potentially important regulators and markers: firstly, the magnitude of fold-change of upregulation; secondly, the contrasted pattern of differential expression between OV, RGC and RPE lineages. We found that among the most highly overexpressed TF-encoding genes in the OV/RGC lineage were three members of the Collier/Olfactory-1/Early B-cell family: EBF1, EBF2 and EBF3. Knockdown of EBF1 led to significant impairment of differentiation of hiPSCs into RGCs. EBF1 was shown to act upstream of ISL1 and BRN3A, the well-characterized regulators of RGC lineage specification. TF-encoding genes DLX1, DLX2 and INSM1 were the most highly overexpressed genes in the OVs, indicating their important role in the early stages of retinal differentiation. Along with MITF, the two paralogs, BHLHE41 and BHLHE40, were the most robust TF markers of RPE cells. The markedly contrasted expression of ACTL6B, encoding the component of chromatin remodeling complex SWI/SNF, discriminated hiPSC-derived OV/RGC and RPE lineages. We identified novel, potentially important intrinsic regulators of RGC and RPE cell lineage specification in the process of differentiation from hiPSCs. We demonstrated the crucial role played by EBF1 in differentiation of RGCs. We identified intrinsic regulator biomarker signatures of these two retinal cell types that can be applied with high confidence to confirm the cell lineage identities.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 37 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 24%
Student > Doctoral Student 4 11%
Student > Bachelor 4 11%
Student > Ph. D. Student 4 11%
Other 3 8%
Other 4 11%
Unknown 9 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 41%
Medicine and Dentistry 3 8%
Agricultural and Biological Sciences 3 8%
Nursing and Health Professions 1 3%
Neuroscience 1 3%
Other 1 3%
Unknown 13 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 May 2018.
All research outputs
#17,951,499
of 23,051,185 outputs
Outputs from Stem Cell Research & Therapy
#1,602
of 2,431 outputs
Outputs of similar age
#236,007
of 325,557 outputs
Outputs of similar age from Stem Cell Research & Therapy
#45
of 68 outputs
Altmetric has tracked 23,051,185 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,431 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 325,557 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.