Faculty Opinions recommendation of Discovery of two GLP-1/Notch target genes that account for the role of GLP-1/Notch signaling in stem cell maintenance.

A stem cell’s immediate microenvironment creates an essential “niche” to maintain stem cell self-renewal. Many niches and their intercellular signaling pathways are known, but for the most part, the key downstream targets of niche signaling remain elusive. Here, we report the discovery of two GLP-1/Notch target genes, lst-1 (lateral signaling target) and sygl-1 (synthetic Glp), that function redundantly to maintain germ-line stem cells (GSCs) in the nematode Caenorhabditis elegans. Whereas lst-1 and sygl-1 single mutants appear normal, lst-1 sygl-1 double mutants are phenotypically indistinguishable from glp-1/Notch mutants. Multiple lines of evidence demonstrate that GLP-1/Notch signaling activates lst-1 and sygl-1 expression in GSCs within the niche. Therefore, these two genes fully account for the role of GLP-1/Notch signaling in GSC maintenance. Importantly, lst-1 and sygl-1 are not required for GLP-1/Notch signaling per se. We conclude that lst-1 and sygl-1 forge a critical link between Notch signaling and GSC maintenance.

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The role of autophagy in morphogenesis and stem cell maintenance

Histochemistry and Cell Biology ◽

10.1007/s00418-018-1751-0 ◽

2018 ◽

Vol 150 (6) ◽

pp. 721-732 ◽

Cited By ~ 5

Author(s):

Eric Bekoe Offei ◽

Xuesong Yang ◽

Beate Brand-Saberi

Keyword(s):

Stem Cell ◽

Stem Cell Maintenance ◽

Cell Maintenance

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Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling

Cells ◽

10.3390/cells9102175 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2175

Author(s):

Adam J. Poe ◽

Mangesh Kulkarni ◽

Aleksandra Leszczynska ◽

Jie Tang ◽

Ruchi Shah ◽

...

Keyword(s):

Wound Healing ◽

Stem Cell ◽

Fine Tuning ◽

Regulatory Role ◽

Human Cornea ◽

Notch 1 ◽

Stem Cell Maintenance ◽

Limbal Epithelium ◽

Cell Maintenance

MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation. Our results provide insights into the regulatory network of miR-146a and its role in fine-tuning of Notch-1 and Notch-2 expressions in limbal epithelium, which could be a balancing factor in stem cell maintenance and differentiation.

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Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance

Developmental Biology ◽

10.1016/j.ydbio.2014.12.033 ◽

2015 ◽

Vol 399 (2) ◽

pp. 226-236 ◽

Cited By ~ 14

Author(s):

Kaitlin M. Laws ◽

Leesa L. Sampson ◽

Daniela Drummond-Barbosa

Keyword(s):

Stem Cell ◽

Adiponectin Receptor ◽

Germline Stem Cell ◽

Receptor Signaling ◽

Stem Cell Maintenance ◽

Cell Maintenance

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The Importance of Ubiquitination and Deubiquitination in Cellular Reprogramming

Stem Cells International ◽

10.1155/2016/6705927 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 33

Author(s):

Bharathi Suresh ◽

Junwon Lee ◽

Kye-Seong Kim ◽

Suresh Ramakrishna

Keyword(s):

Stem Cell ◽

Transcription Factors ◽

Embryonic Stem ◽

Cellular Reprogramming ◽

Stem Cell Maintenance ◽

Opposite Action ◽

Induced Pluripotent ◽

Related Proteins ◽

Cell Maintenance

Ubiquitination of core stem cell transcription factors can directly affect stem cell maintenance and differentiation. Ubiquitination and deubiquitination must occur in a timely and well-coordinated manner to regulate the protein turnover of several stemness related proteins, resulting in optimal embryonic stem cell maintenance and differentiation. There are two switches: an E3 ubiquitin ligase enzyme that tags ubiquitin molecules to the target proteins for proteolysis and a second enzyme, the deubiquitinating enzyme (DUBs), that performs the opposite action, thereby preventing proteolysis. In order to maintain stemness and to allow for efficient differentiation, both ubiquitination and deubiquitination molecular switches must operate properly in a balanced manner. In this review, we have summarized the importance of the ubiquitination of core stem cell transcription factors, such as Oct3/4, c-Myc, Sox2, Klf4, Nanog, and LIN28, during cellular reprogramming. Furthermore, we emphasize the role of DUBs in regulating core stem cell transcriptional factors and their function in stem cell maintenance and differentiation. We also discuss the possibility of using DUBs, along with core transcription factors, to efficiently generate induced pluripotent stem cells. Our review provides a relatively new understanding regarding the importance of ubiquitination/deubiquitination of stem cell transcription factors for efficient cellular reprogramming.

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