Human bone marrow multipotent mesenchymal stromal cells (hMSCs) number decreases with aging. Sub-populations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues, and participate in their repair. Maintaining throughout adult life, such cell sub-populations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox 2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain (NICD), notch target genes, neuronal transcriptional repressor element 1 (RE1) silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1). Additionally, by decreasing the expression of (i) the pro-apoptotic proteins apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity. Furthermore, low oxygen increases canonical Wnt pathway signaling, co-receptor Lrp5 expression, and PI3K/Akt pathway activation. Lrp5 inhibition decreases self-renewal marker Sox2 mRNA, Oct4a nuclear accumulation and cell numbers. Wortmannin-mediated PI3K/Akt pathway inhibition leads to increased osteoblastic differentiation at both, low and high, oxygen tensions. We demonstrate that low oxygen stimulates a complex signaling network involving PI3K/Akt, Notch, and canonical Wnt pathways, which mediate the observed increase in nuclear Oct4a and REST, with simultaneous decrease in p53, AIF and Bak. Collectively, these pathway activations contribute to increased self-renewal with concomitant decreased differentiation, cell cycle arrest, apoptosis and/or senescence in MIAMI cells. Importantly, the PI3K/Akt pathway plays a central mechanistic role in the oxygen tension-regulated self-renewal vs. osteoblastic differentiation of progenitor cells.
Pharmacology, Toxicology and Pharmaceutical Science
2
4%
Engineering
2
4%
Other
6
12%
Unknown
13
26%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 18 May 2016.
All research outputs
#22,632,100
of 34,763,505 outputs
Outputs from Stem Cells & Development
#1,380
of 2,043 outputs
Outputs of similar age
#199,955
of 341,041 outputs
Outputs of similar age from Stem Cells & Development
#21
of 36 outputs
Altmetric has tracked 34,763,505 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,043 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
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We're also able to compare this research output to 36 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.
