Matches in SemOpenAlex for { <https://semopenalex.org/work/W4300002796> ?p ?o ?g. }
- W4300002796 abstract "Ongoing cell replacement studies and clinical trials have demonstrated the need to control donor and newborn cell behavior within their target tissue. Here we present a methodology to guide stem cell-derived and endogenously regenerated neurons by engineering the microenvironment. Being an “approachable part of the brain,” the eye provides a unique opportunity to study donor neuron fate, migration, and integration within the central nervous system. Glaucoma and other optic neuropathies lead to the permanent loss of retinal ganglion cells (RGCs) – the neurons in the retina that transfer all visual information from the eye to the brain. Cell transplantation and transdifferentiation strategies have been proposed to restore RGCs, and one of the significant barriers to successful RGC integration into the existing retinal circuitry is cell migration towards their natural position in the retina. Here we describe a framework for identifying, selecting, and applying chemokines to direct cell migration in vivo within the retina. We have performed an in silico analysis of the single-cell transcriptome of the developing human retina and identified six receptor-ligand candidates to guide stem cell-derived or newborn neurons. The lead candidates were then tested in functional in vitro assays for their ability to guide stem cell-derived RGCs. For the in vivo studies, donor and newborn neurons were differentiated in human and mouse retinal organoids or endogenously reprogrammed with proneuronal transcription factors, respectively. An exogenous stromal cell-derived factor-1 (SDF1) gradient led to a 2.7-fold increase in donor RGC migration into the ganglion cell layer and a 3.3-fold increase in the displacement of newborn RGCs out of the inner nuclear layer. Furthermore, by altering the migratory profile of donor RGCs toward multipolar migration, overall migration was improved in mature retinal tissues. Together, these results highlight the ability and importance of engineering the tissue microenvironment and the individual cells for research and clinical applications in gene and cell therapies. Graphical Abstract In brief, the “in silico – in vitro – in vivo” funnel holds significant potential for identifying targets to control cellular processes in research and clinical applications. In this report, Soucy et al. describes a framework for identifying, selecting, and applying chemokines to direct retinal ganglion cell migration in vivo within the adult mouse retina." @default.
- W4300002796 created "2022-10-03" @default.
- W4300002796 creator A5026497763 @default.
- W4300002796 creator A5038440605 @default.
- W4300002796 creator A5063559360 @default.
- W4300002796 creator A5067265153 @default.
- W4300002796 creator A5068161443 @default.
- W4300002796 creator A5083336047 @default.
- W4300002796 date "2022-10-01" @default.
- W4300002796 modified "2023-10-01" @default.
- W4300002796 title "Introduced chemokine gradients guide transplanted and regenerated retinal neurons toward their natural position in the retina" @default.
- W4300002796 cites W1487547430 @default.
- W4300002796 cites W1967124592 @default.
- W4300002796 cites W1983652118 @default.
- W4300002796 cites W1992466747 @default.
- W4300002796 cites W2025579230 @default.
- W4300002796 cites W2034429149 @default.
- W4300002796 cites W2036245829 @default.
- W4300002796 cites W2041598409 @default.
- W4300002796 cites W2049956106 @default.
- W4300002796 cites W2053483510 @default.
- W4300002796 cites W2058826061 @default.
- W4300002796 cites W2067483360 @default.
- W4300002796 cites W2069089843 @default.
- W4300002796 cites W2074314696 @default.
- W4300002796 cites W2075871987 @default.
- W4300002796 cites W2081407876 @default.
- W4300002796 cites W2083452535 @default.
- W4300002796 cites W2093304039 @default.
- W4300002796 cites W2094203217 @default.
- W4300002796 cites W2103656923 @default.
- W4300002796 cites W2104315509 @default.
- W4300002796 cites W2108504850 @default.
- W4300002796 cites W2112798265 @default.
- W4300002796 cites W2115929153 @default.
- W4300002796 cites W2123879591 @default.
- W4300002796 cites W2124977640 @default.
- W4300002796 cites W2131016346 @default.
- W4300002796 cites W2136373690 @default.
- W4300002796 cites W2147656680 @default.
- W4300002796 cites W2160605010 @default.
- W4300002796 cites W2165567772 @default.
- W4300002796 cites W2166663391 @default.
- W4300002796 cites W2169536434 @default.
- W4300002796 cites W2176746291 @default.
- W4300002796 cites W2193602046 @default.
- W4300002796 cites W2229551171 @default.
- W4300002796 cites W2313749244 @default.
- W4300002796 cites W2318035006 @default.
- W4300002796 cites W2326860902 @default.
- W4300002796 cites W2332292689 @default.
- W4300002796 cites W2537731554 @default.
- W4300002796 cites W2539197373 @default.
- W4300002796 cites W2549085969 @default.
- W4300002796 cites W2554188938 @default.
- W4300002796 cites W2606387395 @default.
- W4300002796 cites W2610588654 @default.
- W4300002796 cites W2760899661 @default.
- W4300002796 cites W2761739377 @default.
- W4300002796 cites W2775484513 @default.
- W4300002796 cites W2783942613 @default.
- W4300002796 cites W2794521141 @default.
- W4300002796 cites W2885100818 @default.
- W4300002796 cites W2889326414 @default.
- W4300002796 cites W2910720451 @default.
- W4300002796 cites W2962809976 @default.
- W4300002796 cites W2990637106 @default.
- W4300002796 cites W2999940498 @default.
- W4300002796 cites W3005472012 @default.
- W4300002796 cites W3011274305 @default.
- W4300002796 cites W3036431915 @default.
- W4300002796 cites W3040538810 @default.
- W4300002796 cites W3089314931 @default.
- W4300002796 cites W3106188259 @default.
- W4300002796 cites W3110220146 @default.
- W4300002796 cites W3116618454 @default.
- W4300002796 cites W3123185162 @default.
- W4300002796 cites W3133762749 @default.
- W4300002796 cites W3206340131 @default.
- W4300002796 cites W3213857759 @default.
- W4300002796 cites W4223491796 @default.
- W4300002796 cites W4240034315 @default.
- W4300002796 cites W4254687493 @default.
- W4300002796 cites W4288056376 @default.
- W4300002796 doi "https://doi.org/10.1101/2022.09.29.510158" @default.
- W4300002796 hasPublicationYear "2022" @default.
- W4300002796 type Work @default.
- W4300002796 citedByCount "2" @default.
- W4300002796 countsByYear W43000027962022 @default.
- W4300002796 countsByYear W43000027962023 @default.
- W4300002796 crossrefType "posted-content" @default.
- W4300002796 hasAuthorship W4300002796A5026497763 @default.
- W4300002796 hasAuthorship W4300002796A5038440605 @default.
- W4300002796 hasAuthorship W4300002796A5063559360 @default.
- W4300002796 hasAuthorship W4300002796A5067265153 @default.
- W4300002796 hasAuthorship W4300002796A5068161443 @default.
- W4300002796 hasAuthorship W4300002796A5083336047 @default.
- W4300002796 hasBestOaLocation W43000027961 @default.
- W4300002796 hasConcept C126322002 @default.
- W4300002796 hasConcept C1491633281 @default.