Selective differentiation of central nervous system-derived stem cells in response to cues from specific regions of the developing brain.
OBJECTIVE
Each region of the brain is distinguished by specific and distinct markers and functions. The authors hypothesized that each region possesses unique trophic properties that dictate and maintain its development. To test this hypothesis, they isolated central nervous system (CNS) stem cells from fetal rodents, and these rat CNS-derived stem cells (RSCs) were placed in coculture with primary cultures of the developing neonatal hippocampus and hypothalamus to determine whether region-specific primary cells would direct the differentiation of stem cells in a region-specific manner.


METHODS
Primary cultures were first established from the neonatal (3-7 days postnatal) hippocampus and hypothalamus. Rodent CNS stem cells, which had been genetically engineered to express green fluorescent protein, were then placed in coculture with the primary CNS cells. The expression of region-specific markers in the RSCs was then evaluated after 2 weeks using immunocytochemistry. Data from previous studies have indicated that primary adult cells lack a differentiation-inducing capacity.


RESULTS
When placed in coculture with primary CNS cells, RSCs began to express both neuronal (MAP2) and glial (glial fibrillary acidic protein) markers. Those that were placed in coculture with hippocampal cells expressed region-specific markers such as gamma-aminobutyric acid, whereas those placed in coculture with hypothalamic cells expressed growth hormone-releasing hormone primarily in the hypothalamus. Conclusions. Pluripotential RSCs were induced to express region-specific phenotypes on coculture with primary cells derived from the developing hippocampus and hypothalamus. The differentiation of RSCs into specific lineages on exposure to specific cell types is likely modulated through direct cell-cell contact. Secreted factors from the primary neural cells may also play a role in this induction. Such a differentiation influence is also likely age dependent.
Vorasubin
Bonnie
B
Division of Neurological Surgery, Veterans Administration San Diego Health Care System, California, USA.
Weedin
John
J
Saljooque
Farid
F
Wilkes
Nathan
N
Eng
M
M
U
Hoi Sang
HS
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D018920:Coculture Techniques; D053686:Fetal Stem Cells / Q000166:cytology* / Q000378:metabolism; D005818:Genetic Engineering / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D005680:gamma-Aminobutyric Acid