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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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P2X7 receptor signaling during adult hippocampal neurogenesis

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Neural Regeneration Research 2019年第10期14卷 1684-1694页

作者： Hannah C. Leeson tailoi chan-ling Michael D. Lovelace Jeremy C. Brownlie Ben J. Gu Michael W. Weible II Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQueenslandAustralia Griffith Institute for Drug Discovery Griffith UniversityBrisbaneQueenslandAustralia Discipline of Anatomy and Histology School of Medical ScienceThe University of SydneySydneyNew South WalesAustralia Bosch Institute The University of SydneySydneyNew South WalesAustralia Applied Neurosciences Program Peter Duncan Neurosciences Research UnitSt. Vincent’s Centre for Applied Medical ResearchSydneyNew South WalesAustralia Faculty of Medicine St. Vincent’s Clinical SchoolUniversity of New South Wales SydneySydneyNew South WalesAustralia School of Environment and Science Griffith UniversityBrisbaneQueenslandAustralia Florey Institute of Neuroscience and Mental Health University of MelbourneMelbourneVictoriaAustralia

Neurogenesis is a persistent and essential feature of the adult mammalian *** neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new *** of hippocampal neurogenesis is complex and multifaceted,and numerous signaling pathways converge to modulate cell proliferation,apoptosis,and clearance of cellular debris,as well as synaptic integration of newborn immature *** expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored.P2X7 receptors are exceptionally versatile:in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation.P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication,and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form,which induce apoptotic cell death through cytosolic ion ***,as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis,as well as during some disease *** how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative *** review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus,and neural stem and progenitor cells.

关键词： P2X7 P2X7R adult neurogenesis neural stem cells neural progenitor cells hippocampus SGZ calcium signaling purinergic signaling

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