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Graphical Abstracts



Laser confocal image of limbal epithelial progenitor cell cluster comprising cytokeratin 15 (CK15)-positive epithelial progenitor cells (turquoise) and associated niche cells, i.e. Melan-A-positive melanocytes (yellow-green) and vimentin-positive subepithelial stromal cells (red) and intraepithelial immune cells (red); nuclei are counterstained with DAPI (blue).

Ubiquitin-ligase Nedd4 down regulates Pax7 levels in a cell context-dependent manner, allowing progression through the myogenic program in adult muscle progenitors.

Production of anti-HER2 antibodies (red) by neural stem cells and their binding (yellow arrows) to the surface of HER2-positive brain metastatic breast cancer cells (green).

Deficiency of BRM-SWI/SNF favors osteoblast lineage selection and confers resistance to osteoporosis. The SWI/SNF chromatin-remodeling complex contains either brahma-related gene-1 (BRG1) or brahma (BRM) as the catalytic ATPase, and functions as a master regulator of gene expression. BRG1 is required for tissuespecific gene expression throughout development, but comparatively little is known about the alternative ATPase, BRM, because BRM-null mice develop normally. The present study now indicates that BRMSWI/SNF plays a key role in lineage selection at the osteoblast vs adipocyte decision point. Rather than favoring tissue-specific gene expression generally, BRM-SWI/SNF represses osteogenic gene expression and promotes adipogenic gene expression. The bone marrow stromal cell (BMSC) population in BRM-null mice contains an increased percentage of osteoblast precursors, at the expense of cells able to differentiate along the adipocyte lineage. This is significant in conditions of osteoblast insufficiency, such that BRM-null mice are resistant to age-related osteoporosis.

W8B2+ cardiac resident stem cells (CRSCs) can be isolated from adult human atrial appendages using explant culture and enriched by fluorescence-activated cell sorting. Human W8B2+ CRSCs exhibit powerful paracrine activity in vitro and are cardioprotective when transplanted into the infarcted myocardium of immunocompromised rats.

miRNA target site enrichment analysis by Sylamer performed on the sorted gene list of expression changes at Day 14 compared to Day 0 revealed significant enrichment of miR-140-5p seed sequences (AACCACT, blue line) in the down-regulated genes during chondrogenesis.

 Human pluripotent stem cell (hPSC) fate is orchestrated by complex interactions between the biophysical and biochemical cues of the cellular microenvironment. This concise review explores how generation of functional hPSC-derived cells for regenerative medicine may come from a better understanding of how mechanobiological factors complement biochemical cues in regulating hPSC pluripotency and directing differentiation.

Low expression of HLA molecules in human iPSC-MSCs under the stimulation of IFN-γ in vitro, and less inflammation and more cell survival after be transplanted into humanized mice. After the stimulation of IFN-γ, a low amount of STAT1 is phosphorylated and there is low IRF-1 and CIITA expression in human iPSC-MSCs. Next, low levels of CIITA are transcripted due to the low level of IRF-1 and the low number of p-STAT1 dimers. Consequently, there is an insufficient amount of CIITA proteins to induce the expression of HLA-II molecules. Less inflammation and more cell survival are found after the transplantation of human iPSC-MSCs into humanized mice.

Overexpression of Hk2 and Pkm2 enables ESCs to maintain high glycolytic flux. Sustaining high glycolytic flux during differentiation prevents ESCs from complete differentiation and allowing them to retain self-renewal potential or pluripotency.

Here we report a time-resolved, global proteomic map of cellular change during the directed differentiation of mouse ES cells into extraembryonic endoderm-like cells induced by forced GATA factor expression. This study reveals that transition from the pluripotent to the differentiated state is accompanied by the downregulation of chromatin-modifying enzymes and cell-cell adhesion molecules, and by the successive upregulation of proteins involved in extracellular matrix biogenesis, membrane trafficking and the tricarboxylic acid cycle, as well as an increase in MAPK.