A comparative study of the neural stem cell niche in the adult hypothalamus of human, mouse, rat and gray mouse lemur (Microcebus murinus)

Abstract

The adult brain contains niches of neural stem cells that continuously add new neurons to selected circuits throughout life. Two niches have been extensively studied in various mammalian species including humans, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus. Recently, studies conducted mainly in rodents have identified a third neurogenic niche in the adult hypothalamus. In order to evaluate whether a neural stem cell niche also exists in the adult hypothalamus in humans, we performed multiple immunofluorescence labeling to assess the expression of a panel of neural stem/progenitor cell (NPC) markers (Sox2, nestin, vimentin, GLAST, GFAP) in the human hypothalamus and compared them with the mouse, rat and a non-human primate species, the gray mouse lemur (Microcebus murinus). Our results show that the adult human hypothalamus contains four distinct populations of cells that express the five NPC markers: (a) a ribbon of small stellate cells that lines the third ventricular wall behind a hypocellular gap, similar to that found along the lateral ventricles, (b) ependymal cells, (c) tanycytes, which line the floor of the third ventricle in the tuberal region, and (d) a population of small stellate cells in the suprachiasmatic nucleus. In the mouse, rat and mouse lemur hypothalamus, co-expression of NPC markers is primarily restricted to tanycytes, and these species lack a ventricular ribbon. Our work thus identifies four cell populations with the antigenic profile of NPCs in the adult human hypothalamus, of which three appear specific to humans.

Musashi‐2 and related stem cell proteins in the mouse suprachiasmatic nucleus and their potential role in circadian rhythms

“…Furthermore, Notch signaling through glial cells has been implicated in regulating memory impairments from sleep loss in Drosophila (Miller et al, 2009). Note, however, that a previous immunochemical study of perfused tissue did not see co‐expression of SOX2 with nestin or vimentin in mouse SCN (Pellegrino et al, 2018), whereas we observed about 5% of cells in explant cultures co‐expressing SOX2 and vimentin.…”

“…Explant cultures prepared from mice of different genetic backgrounds indicated stem‐like SCN cells are not limited to B6 mice and are likely found in other species. A publication that appeared after our work was completed, provided evidence that the adult human SCN contains stem‐like cells, suggesting that this may be a general property of the brain clock (Pellegrino et al, 2018). Studies exploring what factors maintain the immature state of SCN cells are aided by the knowledge that circadian rhythms persist in SPM; interaction between circadian clock components and stem cell‐related genes may provide insight into cell differentiation.…”

“…Evidence of the adult SCN's partially undifferentiated state includes cells expressing SOX2, an important regulatory protein in embryonic and adult neural stem cells (Hoefflin and Carter, 2014; Pellegrino et al, 2018), and doublecortin (DCX), a marker for immature cells such as neuroblasts committed to further differentiation into neurons (Walker et al, 2007; Geoghegan and Carter, 2008). DCX‐expressing cells were described in the SCN's core region and co‐localized with neurons expressing vasoactive intestinal polypeptide (VIP) or gastrin‐releasing peptide (GRP)(Geoghegan and Carter, 2008).…”

Tanycytes: A rich morphological history to underpin future molecular and physiological investigations

“…205,206 Subsequent to these pioneering works, a series of investigations and reviews supported the contention that neurones and glial cells are generated from local NSC in the hypothalamus throughout life. 58,[207][208][209][210][211][212][213][214][215] What is the source of these new neurones? Increasing evidence has shown that tanycytes exhibit NSC properties.…”

Are Tanycytes the Missing Link Between Type 2 Diabetes and Alzheimer’s Disease?

“…Most recently, Pellegrino et al have reported on a comparative study of the neural stem cell niche in the adult hypothalamus of human, mouse rat and gray mouse lemur using a panel of 5 neural stem/progenitor cell (NPCs)-specific markers including Sox2, Nestin, Vimentin, GLAST and GFAP [55]. Their data suggest that unlike the mouse, rat and the gray mouse lemur, adult human hypothalamus contains 4 different NPC cell types express including a ribbon of small stellate cells lining the third ventricular wall, ependymal cells, tanycytes and a population of small stellate cells in the suprachiasmatic nucleus.…”