The HOPX and BLBP landscape and gliogenic regions in developing human brain

Camilla Bjørnbak Holst, Christian Beltoft Brøchner, Kristoffer Vitting-Seerup, Kjeld Møllgård*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Outer radial glial cells (oRGs) give rise to neurons and glial cells and contribute to cell migration and expansion in developing neocortex. HOPX has been described as a marker of oRGs and possible actor in glioblastomas. Recent years' evidence points to spatiotemporal differences in brain development which may have implications for the classification of cell types in the central nervous system and understanding of a range of neurological diseases. Using the Human Embryonic/Fetal Biobank, Institute of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, HOPX and BLBP immunoexpression was investigated in developing frontal, parietal, temporal and occipital human neocortex, other cortical areas and brain stem regions to interrogate oRG and HOPX regional heterogeneity. Furthermore, usage of high-plex spatial profiling (Nanostring GeoMx® DSP) was tested on the same material. HOPX marked oRGs in several human developing brain regions as well as cells in known gliogenic areas but did not completely overlap with BLBP or GFAP. Interestingly, limbic structures (e.g. olfactory bulb, indusium griseum, entorhinal cortex, fimbria) showed more intense HOPX immunoreactivity than adjacent neocortex and in cerebellum and brain stem, HOPX and BLBP seemed to stain different cell populations in cerebellar cortex and corpus pontobulbare. DSP screening of corresponding regions indicated differences in cell type composition, vessel density and presence of apolipoproteins within and across regions and thereby confirming the importance of acknowledging time and place in developmental neuroscience.

OriginalsprogEngelsk
TidsskriftJournal of Anatomy
Vol/bind243
Udgave nummer1
Sider (fra-til)23-38
Antal sider16
ISSN0021-8782
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We would like to thank Pernille S. Froh, Ha Nguyen and Keld B. Ottosen, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, for excellent technical assistance. We would also like to thank Dr. Rudy van Eijsden, NanoString Technologies, for advice and assistance with interpretation and normalization of Nanostring GeoMx DSP data. Furthermore, we acknowledge the Core Facility for Integrated Microscopy (CFIM), Faculty of Health and Medical Sciences, University of Copenhagen, for expert assistance. This work was supported by a Graduate Scholarship from The Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (C. B. H.), a grant from Læge Sofus Carl Emil Friis og hustru Olga Doris Friis' Legat (C. B. B.) and Vera and Carl Johan Michaelsen Foundation (#34077 to K. M.; C.B.H). The authors have no conflicts of interest to declare. ®

Publisher Copyright:
© 2023 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

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