Researchers Discover “Gorditas” and Other Unheard Types of Brain Cells

According to a study published June 20 in Science, scientists discovered two types of glial cells in the brains of adult mice – an astrocyte and an oligodendrocyte progenitor cell – after pushing neural stem cells to rise from dormancy. The results indicate new roles for glial cells, notorious for offering support to neurons. They also can prompt a much better understanding of how brains remain plastic right into the adult years when the substantial majority of neurons do not experience cellular division.

Arturo Alvarez-Buylla, a developmental neuroscientist at the College of The Golden State, San Francisco, states that this study is a vital addition to the whole story about these fascinating [stem] cells in the adult brain of rodents that can produce new cells. He was not involved with the study; however, he says that understanding adult stem cells is essential to understand the types of plasticity that exist after the developmental period ends.

Many mammalian brain cells, be they neurons or glia, are generated throughout embryonic development, and reserves of stem cells become grossly, otherwise ultimately, dormant in their adult years. The little stream of activity left can help the brain respond to transform, in some cases by creating new neurons to help with discovering or by producing cells in feedback to injury or condition.

One group exists in the brains of adult humans and mice in a section called the ventricular-subventricular zone (V-SVZ). The walls of the two lateral ventricles, gaps filled with cerebrospinal fluid, are lined with stem cells. Along these walls, the cells have a regional identity – where a stem cell rests on the wall dictates what it differentiates into. This function has been well-characterized for neuronal subtypes synthesized within distinct domains on the sidewall. Glial cells are admittedly created at low stages along the septal wall, but specific subtypes continue to be unknown since the cells along this wall typically continue to be inactive.

Adult stem cells and the variables that control their inactivity, or quiescence, have long amazed Fiona Doetsch – a stem cell biologist and a neuroscientist at the College of Basel in Switzerland, who co-authored the research study. On The Scientist, Doetsch explains that people perceived quiescent cells as cells hiding out and being insensitive to any signals when, in reality, the quiescent state is emerging as a very actively maintained state.

To determine what might be preserving these stem cells in a quiescent state, Doetsch first contrasted the transcriptomes of purified inactive and activated stem cells from the V-SVZ of adult mice. Approximately 95 percent of the quiescent cells had high degrees of a receptor called platelet-derived growth factor-beta (PDGFRβ), compared to only half of the activated stem cells. This idea led Doetsch to presume that annoying the PDGFRβ signal might launch stem cells from dormancy.

The ligands cannot bind the developed mouse model with an altered PDGFRβ and marked adult V-SVZ stem cells with a fluorescent protein to track any new cells created by the stem cells.

As anticipated, the silencing of PDGFRβ caused an increase in active and separating stem cells in both sections of the V-SVZ compared to control mice. This resurgence led to the discovery of more mature neurons in the olfactory bulb and more oligodendrocytes, a kind of glial cell, in the adjacent corpus callosum. The olfactory neurons were detected on the lateral wall, while the oligodendrocytes originated from the septal wall. Fluorescing cells were spotted beyond the ventricles for more than 180 days, a sign that the new cells lingered and incorporated into the brain.

The experiment prompted Doetsch’s team to identify two types of undocumented glial cells. One domain on the septal wall generated a kind of astrocyte – suggested by molecular indicators characteristic of this cell type – that the researchers called gorditas because of their stocky and round cell bodies that are smaller than known astrocytes, which have a bushy appearance.

The team also determined several domains that generated oligodendrocytes. The domains include an area situated at the edge of the ventricle that generated oligodendrocyte progenitor cells (OPCs), an intermediate between stem cells and mature oligodendrocytes. It is unusual, Doetsch informs The Scientist, for these cells to be connected to the surface area of the ventricle wall as opposed to buried in brain tissue. “Nobody expected them to be inside the ventricular system as well as attached to the wall of the ventricle. Therefore nobody had ever looked there before,” Doetsch says. “However, when you look, you can see them wonderfully.”

Doetsch and her group discovered several unusual qualities about the OPCs beyond their choice of real estate. The cells were continually bathed in cerebrospinal liquid, passing between the two side ventricles. While the progenitor cells did not have the characteristic myelin sheath that grows oligodendrocytes make use of to insulate the axons of neurons, these intermediary cells were still intertwined with the axons of neurons expanding from brain areas far away from the V-SVZ.

None of these progenitor cells differentiated right into fully grown oligodendrocytes during the experiment – one more rarity states Sarah Moyon, a neuroscientist at the City University of New york city that researches oligodendrocytes and is not involved in this research. “Their setting, where they are, and also the reality that. We do not see them discolor” for classic indicators of adult oligodendrocytes all indicate that these cells have a motive for remaining as progenitors, with their own particular and as-yet-unidentified function, she includes.

Given their contact with both the cerebrospinal fluid and long-range axons, both Moyon and Doetsch inform The Scientist that they think the OPCs play some role in neural interaction. “They’re distinctly positioned to gauge and integrate signals from different brain regions,” Doetsch says. “We are very interested now in specifying the receptors that they express as well as what sort of information cells exchange.”

Since a majority of V-SVZ stem cells are inactive under ordinary circumstances, the team performed one last experiment to see whether the injury might lead the cells to activate naturally. They injected a compound called lysolecithin that deteriorates myelin in the corpus callosum of wild-type mice. In return, stem cells along the septal wall surface began creating even more, OPCs and gordita astrocytes, although the scientists did not detect whether the cells migrated to the corpus callosum, a step for future studies.

While this study was performed on mice, human beings have comparable brain regions. “Since we comprehend this modulator of [stem cells] quiescence in mice, maybe one could evaluate whether it is similarly present in humans. We do not know yet if these oligodendrocyte progenitors are present there,” Doetsch informs The Scientist. “We understand so little concerning them, and also, there is still a great deal to find.”

Read the original article.