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BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

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Neural Regeneration Research 2024年第2期19卷 447-457页

作者： Michael W.Weible II Michael D.Lovelace Hamish D.Mundell tsz wai rosita pang Tailoi Chan-Ling Bosch Institute Discipline of Anatomy and Histology(F13)University of SydneySydneyNSWAustralia School of Environment and Science Griffith UniversityNathanQLDAustralia Discipline of Medicine Nepean Clinical SchoolFaculty of Medicine and HealthUniversity of SydneyKingswoodNSWAustralia New South Wales Brain Tissue Resource Centre School of Medical SciencesFaculty of Medicine and HealthUniversity of SydneyCharles Perkins Centre(D17)SydneyNSWAustralia

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well ***-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is *** was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory *** and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/*** immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,*** neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent *** cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage ***-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in *** is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal *** data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterize

关键词： BMPRⅡ bone morphogenetic protein histotypic human spinal cord development leukemia inhibitory factor neurosphere organotypic reaggregate sensory columns

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