SSEA‐4 and YKL‐40 positive progenitor subtypes in the subventricular zone of developing human neocortex

Abstract

The glycosphingolipid SSEA‐4 and the glycoprotein YKL‐40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA‐4 and YKL‐40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double‐labeling immunofluorescence. A few small rounded SSEA‐4 and YKL‐40 labeled cells were present in the radial glial BLBP positive proliferative zones adjacent to the lateral ganglionic eminence from 12th week post conception. With increasing age, a similarly stained cell population appeared more widespread in the subventricular zone. At midgestation, the entire subventricular zone showed patches of SSEA‐4, YKL‐40, and BLBP positive cells. Co‐labeling with markers for radial glial cells (RGCs) and neuronal, glial, and microglial markers tested the lineage identity of this subpopulation of radial glial descendants. Adjacent to the ventricular zone, a minor fraction showed overlap with GFAP but not with nestin, Olig2, NG2, or S100. No co‐localization was found with neuronal markers NeuN, calbindin, DCX or with markers for microglial cells (Iba‐1, CD68). Moreover, the SSEA‐4 and YKL‐40 positive cell population in subventricular zone was largely devoid of Tbr2, a marker for intermediate neuronal progenitor cells descending from RGCs. YKL‐40 has recently been found in astrocytes in the neuron‐free fimbria, and both SSEA‐4 and YKL‐40 are present in malignant astroglial brain tumors. We suggest that the population of cells characterized by immunohistochemical combination of antibodies against SSEA‐4 and YKL‐40 and devoid of neuronal and microglial markers represent a yet unexplored astrogenic lineage illustrating the complexity of astroglial development. GLIA 2016;64:90–104

RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis

“…The specimens were dehydrated with graded alcohols, cleared in xylene, and paraffin embedded. Serial sections, 3-10 µm thick, were cut in transverse, sagittal, or horizontal planes, placed on salinized glass slides, and used for immunohistochemical experiments 65 . Immunohistochemical analyses were performed on deparaffinised sections of human brain 19 wpc.…”

“…Immunohistochemical analyses were performed on deparaffinised sections of human brain 19 wpc. Samples were carefully treated in heat-induced antigen retrieval using citrate buffer pH 6.0, prior to blocking of unspecific binding and incubation with primary antibodies overnight 65 . Immunofluorescence staining was prepared as for bright-field microscopy.…”

Astrogliogenesis in human fetal brain: complex spatiotemporal immunoreactivity patterns of GFAP, S100, AQP4 and YKL‐40

“…We have previously found YKL‐40 protein expression in subgroups of possible astroglial progenitors and fetal astrocytes (Bjørnbak et al. ; Brøchner & Møllgård, ). Based on the transcriptome profiling (http://www.brainrnaseq.org) performed by Zhang et al.…”

“…) and we found possible S100‐positive oligodendrocyte precursors along fiber tracts in the brainstem. Apart from combined SSEA‐4 and YKL‐40 staining in astroglial progenitors and astrocytes (Brøchner & Møllgård, ), YKL‐40 has been found in pericytes, leptomeningeal cells and choroid plexus epithelium in developing human brain (Bjørnbak et al. ) and in neurons in adult human brain (results not shown), and has a staining pattern very different from that of other astroglial markers.…”

“…To explore marker distribution and spatiotemporal patterns of early‐stage human astrogliogenesis, we compared immunoexpression of the diverse astroglial markers GFAP, S100 and AQP4 in human developing fetal brain and further included YKL‐40, a glycoprotein, which has been found in possible fetal astrocytes and astroglial progenitors in human developing brain (Bjørnbak et al. ; Brøchner & Møllgård, ), primary cultures of human embryonic astrocytes (Singh et al. ), gliomas (Qin et al.…”