Human Endometrial Reconstitution From Somatic Stem Cells: The Importance of Niche-Like Cells
REPRODUCTIVE SCIENCES
Authors: Lopez-Perez, Nuria; Gil-Sanchis, Claudia; Ferrero, Hortensia; Faus, Amparo; Diaz, Ana; Pellicer, Antonio; Cervello, Irene; Simon, Carlos
Abstract
Endometrial regeneration has long been proposed to be mediated by stem cells, but the isolation of endometrial stem cells has been hampered by a lack of validated markers. Specific markers would enable isolation of these stem cells, thereby promoting advancements in regenerative medicine for the treatment of endometrial diseases and dysfunctions. We sought to investigate the regenerative ability of human endometrial positive for sushi domain containing 2/intercellular adhesion molecule 1 (SUSD2(+)/ICAM1(+)) cells and Side Population cell lines in a xenograft mice model. The injection of total endometrial cell suspensions and Side Population cell lines under kidney capsules induced neoformation of human endometrium verified by the presence of typical endometrial markers (vimentin, cytokeratin 18, and progesterone receptor) by immunofluorescence. Total endometrial cell types promoted a better reconstitution in comparison to injecting ICAM1(+) and SUSD2(+) cells alone. The endometrial fraction is probably acting as a niche, resulting in increased reconstruction efficiency of pure fractions. Human engrafted cells were localized near blood vessels and induced the proliferation of surrounding cells. Our results suggest that human endometrial Side Population, a heterogeneous population possibly harboring endometrial stem cells, has the optimum capacity to regenerate endometrial-like tissue. In contrast, cells positive for single stem cell markers SUSD2 and ICAM1 have minimally functional regenerative capacities in the absence of niche-like cells.
Cell-Surface Proteomics Identifies Differences in Signaling and Adhesion Protein Expression between Naive and Primed Human Pluripotent Stem Cells
STEM CELL REPORTS
Authors: Wojdyla, Katarzyna; Collier, Amanda J.; Fabian, Charlene; Nisi, Paola S.; Biggins, Laura; Oxley, David; Rugg-Gunn, Peter J.
Abstract
Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1,700 plasma membrane proteins, including those involved in cell adhesion, signaling, and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signaling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signaling pathway activity and has identified new markers to define human pluripotent states.