000032201 001__ 32201
000032201 005__ 20210121082901.0
000032201 0247_ $$2doi$$a10.1371/journal.pone.0135830
000032201 0248_ $$2sideral$$a92343
000032201 037__ $$aART-2015-92343
000032201 041__ $$aeng
000032201 100__ $$aWright LS
000032201 245__ $$aVSX2 and ASCL1 are indicators of neurogenic competence in human retinal progenitor cultures
000032201 260__ $$c2015
000032201 5060_ $$aAccess copy available to the general public$$fUnrestricted
000032201 5203_ $$aThree dimensional (3D) culture techniques are frequently used for CNS tissue modeling and organoid production, including generation of retina-like tissues. A proposed advantage of these 3D systems is their potential to more closely approximate in vivo cellular microenvironments, which could translate into improved manufacture and/or maintenance of neuronal populations. Visual System Homeobox 2 (VSX2) labels all multipotent retinal progenitor cells (RPCs) and is known to play important roles in retinal development. In contrast, the proneural transcription factor Acheate scute-like 1 (ASCL1) is expressed transiently in a subset of RPCs, but is required for the production of most retinal neurons. Therefore, we asked whether the presence of VSX2 and ASCL1 could gauge neurogenic potential in 3D retinal cultures derived from human prenatal tissue or ES cells (hESCs). Short term prenatal 3D retinal cultures displayed multiple characteristics of human RPCs (hRPCs) found in situ, including robust expression of VSX2. Upon initiation of hRPC differentiation, there was a small increase in co-labeling of VSX2+ cells with ASCL1, along with a modest increase in the number of PKCa+ neurons. However, 3D prenatal retinal cultures lost expression of VSX2 and ASCL1 over time while concurrently becoming refractory to neuronal differentiation. Conversely, 3D optic vesicles derived from hESCs (hESC-OVs) maintained a robust VSX2+ hRPC population that could spontaneously co-express ASCL1 and generate photoreceptors and other retinal neurons for an extended period of time. These results show that VSX2 and ASCL1 can serve as markers for neurogenic potential in cultured hRPCs. Furthermore, unlike hESC-OVs, maintenance of 3D structure does not independently convey an advantage in the culture of prenatal hRPCs, further illustrating differences in the survival and differentiation requirements of hRPCs extracted from native tissue vs. those generated entirely in vitro.
000032201 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000032201 590__ $$a3.057$$b2015
000032201 591__ $$aMULTIDISCIPLINARY SCIENCES$$b11 / 62 = 0.177$$c2015$$dQ1$$eT1
000032201 592__ $$a1.427$$b2015
000032201 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2015$$dQ1
000032201 593__ $$aMedicine (miscellaneous)$$c2015$$dQ1
000032201 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000032201 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000032201 700__ $$0(orcid)0000-0003-0349-9997$$aPinilla I$$uUniversidad de Zaragoza
000032201 700__ $$aSaha J
000032201 700__ $$aClermont JM
000032201 700__ $$aLien JS
000032201 700__ $$aBorys KD
000032201 700__ $$aCapowski EE
000032201 700__ $$aPhillips MJ
000032201 700__ $$aGamm DM.
000032201 7102_ $$11004$$2646$$aUniversidad de Zaragoza$$bDpto. Cirugía,Ginecol.Obstetr.$$cÁrea Oftalmología
000032201 773__ $$g10, 8 (2015), 0135830 [22p.]$$pPLoS One$$tPloS one$$x1932-6203
000032201 8564_ $$s1183206$$uhttps://zaguan.unizar.es/record/32201/files/texto_completo.pdf$$yVersión publicada
000032201 8564_ $$s109701$$uhttps://zaguan.unizar.es/record/32201/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000032201 909CO $$ooai:zaguan.unizar.es:32201$$particulos$$pdriver
000032201 951__ $$a2021-01-21-08:15:42
000032201 980__ $$aARTICLE