@article {892,
	title = {Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin},
	journal = {Cell Stem Cell},
	volume = {32},
	year = {2025},
	month = {Jan-04-2025},
	pages = {613 - 626.e8},
	abstract = {Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient increase in Aspn expression by the pericryptal fibroblasts induces epithelial transforming growth factor b (TGF-b)-signaling via CD44 and promotes timely epithelial reprogramming. Temporal control of Aspn is lost in old mice, and after damage, the persistently high level of Aspn stagnates epithelium in the regenerative state. Increase in Wnt signaling can resolve the stagnated regenerative program of the old epithelium, promoting restoration of tissue function. In summary, we establish a platform for modeling epithelial injury responses ex vivo and show that the mesenchymal Aspn-producing niche modulates tissue repair by regulating epithelial fetal-like reprogramming.},
	issn = {19345909},
	doi = {10.1016/j.stem.2025.02.009},
	url = {https://www.sciencedirect.com/science/article/pii/S1934590925000487},
	author = {Iqbal, Sharif and Andersson, Simon and Nesta, Ernesta and Pentinmikko, Nalle and Kumar, Ashish and Jha, Sawan K. and Borshagovski, Daniel and Webb, Anna and Gebert, Nadja and Viitala, Emma W. and Ritchie, Alexandra and Scharaw, Sandra and Kuuluvainen, Emilia and Larsen, Hjalte L. and Saarinen, Tuure and Juuti, Anne and Ristim{\"a}ki, Ari and Jeltsch, Michael and Ori, Alessandro and Varjosalo, Markku and Pietil{\"a}inen, Kirsi H. and Ollila, Saara and Jensen, Kim B. and Oudhoff, Menno J. and Katajisto, Pekka}
}
@article {27,
	title = {Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function},
	journal = {FASEB J},
	volume = {17},
	year = {2003},
	month = {2003/Nov/},
	pages = {2006 - 13},
	abstract = {Vascular endothelial cells are characterized by a high degree of functional and phenotypic plasticity, which is controlled both by their pericellular microenvironment and their intracellular gene expression programs. To gain further insight into the mechanisms regulating the endothelial cell phenotype, we have compared the responses of lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs) to vascular endothelial growth factors (VEGFs). VEGFR-3-specific signals are sufficient for LEC but not BEC proliferation, as shown by the ability of the specific ligand VEGF-C156S to stimulate cell cycle entry only in LECs. On the other hand, we found that VEGFR-3 stimulation did not induce LEC cell shape changes typical of VEGFR-2-stimulated LECs, indicating receptor-specific differences in the cytoskeletal responses. Genes induced via VEGFR-2 also differed between BECs and LECs: angiopoietin-2 (Ang-2) was induced via VEGFR-2 in BECs and LECs, but the smooth muscle cell (SMC) chemoattractant BMP-2 was induced only in BECs. Both BECs and LECs were able to promote SMC chemotaxis, but contact with SMCs led to down-regulation of VEGFR-3 expression in BECs in a 3-dimensional coculture system. This was consistent with the finding that VEGFR-3 is down-regulated in vivo at sites of endothelial cell-pericyte/smooth muscle cell contacts. Collectively, these data show intrinsic cell-specific differences of BEC and LEC responses to VEGFs and identify a pericellular regulatory mechanism for VEGFR-3 down-regulation in endothelial cells.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/14597670},
	author = {Veikkola, Tanja and Lohela, Marja and Ikenberg, Kristian and M{\"a}kinen, Taija and Korff, Thomas and Saaristo, Anne and Petrova, Tatania and Jeltsch, Michael and Augustin, Hellmut G and Alitalo, Kari}
}
