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

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