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Mendeley readers
Attention Score in Context
| Title |
Inhibition of the RhoGTPase Cdc42 by ML141 enhances hepatocyte differentiation from human adipose-derived mesenchymal stem cells via the Wnt5a/PI3K/miR-122 pathway: impact of the age of the donor
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|---|---|
| Published in |
Stem Cell Research & Therapy, June 2018
|
| DOI | 10.1186/s13287-018-0910-5 |
| Pubmed ID | |
| Authors |
Diana Chaker, Charbel Mouawad, Albert Azar, Didier Quilliot, Ibrahim Achkar, Ziad Fajloun, Nehman Makdissy |
| Abstract |
Human adipose-derived mesenchymal stem cells (hADSCs) are promising cells that may promote hepatocyte differentiation (Hep-Dif) and improve liver function, but the involvement of Cdc42, a key small RhoGTPase which plays a crucial role in aging, is still not well established. We hypothesized that the inhibition of Cdc42 may rescue the hepatogenic potential of hADSCs derived from aged donors. hADSCs isolated from 61 women of different ages were cultured for evaluation of the proliferation of cells, adherence, apoptosis, immunomodulation, immunophenotyping, multipotency, gene expression, and cell function during Hep-Dif. Inhibition of Cdc42 by ML141 was realized during two phases: initiation (days -2 to 14 (D-2/14)) from undifferentiated to hepatoblast-like cells, or maturation (days 14 to 28 (D14/28)) from undifferentiated to hepatocyte-like cells. Mechanistic insights of the Wnt(s)/MAPK/PI3K/miR-122 pathways were studied. Cdc42 activity in undifferentiated hADSCs showed an age-dependent significant increase in Cdc42-GTP correlated to a decrease in Cdc42GAP; the low potentials of cell proliferation, doubling, adherence, and immunomodulatory ability (proinflammatory over anti-inflammatory) contrary to the apoptotic index of the aged group were significantly reversed by ML141. Aged donor cells showed a decreased potential for Hep-Dif which was rescued by ML141 treatment, giving rise to mature and functional hepatocyte-like cells as assessed by hepatic gene expression, cytochrome activity, urea and albumin production, low-density lipoprotein (LDL) uptake, and glycogen storage. ML141-induced Hep-Dif showed an improvement in mesenchymal-epithelial transition, a switch from Wtn-3a/β-catenin to Wnt5a signaling, involvement of PI3K/PKB but not the MAPK (ERK/JNK/p38) pathway, induction of miR-122 expression, reinforcing the exosomes release and the production of albumin, and epigenetic changes. Inhibition of PI3K and miR-122 abolished completely the effects of ML141 indicating that inhibition of Cdc42 promotes the Hep-Dif through a Wnt5a/PI3K/miR-122/HNF4α/albumin/E-cadherin-positive action. The ML141(D-2/14) protocol had more pronounced effects when compared with ML141(D14/28); inhibition of DNA methylation in combination with ML141(D-2/14) showed more efficacy in rescuing the Hep-Dif of aged hADSCs. In addition to Hep-Dif, the multipotency of aged hADSC-treated ML141 was observed by rescuing the adipocyte and neural differentiation by inducing PPARγ/FABP4 and NeuN/O4 but inhibiting Pref-1 and GFAP, respectively. ML141 has the potential to reverse the age-related aberrations in aged stem cells and promotes their hepatogenic differentiation. Selective inhibition of Cdc42 could be a potential target of drug therapy for aging and may give new insights on the improvement of Hep-Dif. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Mexico | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 43 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 14% |
| Student > Ph. D. Student | 5 | 12% |
| Student > Bachelor | 4 | 9% |
| Student > Master | 4 | 9% |
| Professor | 3 | 7% |
| Other | 8 | 19% |
| Unknown | 13 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 19% |
| Medicine and Dentistry | 7 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 7% |
| Agricultural and Biological Sciences | 2 | 5% |
| Mathematics | 1 | 2% |
| Other | 4 | 9% |
| Unknown | 18 | 42% |
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 01 July 2018.
All research outputs
#15,683,389
of 23,305,591 outputs
Outputs from Stem Cell Research & Therapy
#1,379
of 2,453 outputs
Outputs of similar age
#209,195
of 328,626 outputs
Outputs of similar age from Stem Cell Research & Therapy
#35
of 63 outputs
Altmetric has tracked 23,305,591 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,453 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 33rd percentile – i.e., 33% 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 328,626 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.