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Differential regulation of proliferation and differentiation in neural precursor cells by the Jak pathway.

Authors
Kim, YH; Chung, JI; Woo, HG; Jung, YS; Lee, SH; Moon, CH; Suh-Kim, H; Baik, EJ
Citation
Stem cells, 28(10):1816-1828, 2010
Journal Title
Stem cells
ISSN
0250-6793
Abstract
Neuronal precursor cells (NPCs) are temporally regulated and have the ability to proliferate and differentiate into mature neurons, oligodendrocytes, and astrocytes in the presence of growth factors (GFs). In the present study, the role of the Jak pathway in brain development was investigated in NPCs derived from neurosphere cultures using Jak2 and Jak3 small interfering RNAs and specific inhibitors. Jak2 inhibition profoundly decreased NPC proliferation, preventing further differentiation into neurons and glial cells. However, Jak3 inhibition induced neuronal differentiation accompanied by neurite growth. This phenomenon was due to the Jak3 inhibition-mediated induction of neurogenin (Ngn)2 and NeuroD in NPCs. Jak3 inhibition induced NPCs to differentiate into scattered neurons and increased the expression of Tuj1, microtubule associated protein 2 (MAP2), Olig2, and neuroglial protein (NG)2, but decreased glial fibrillary acidic protein (GFAP) expression, with predominant neurogenesis/polydendrogenesis compared with astrogliogenesis. Therefore, Jak2 may be important for NPC proliferation and maintenance, whereas knocking-down of Jak3 signaling is essential for NPC differentiation into neurons and oligodendrocytes but does not lead to astrocyte differentiation. These results suggest that NPC proliferation and differentiation are differentially regulated by the Jak pathway.
MeSH terms
AnimalsBlotting, WesternBrain/embryologyBrain/metabolismCell Differentiation/drug effects*Cell Differentiation/geneticsCell Proliferation/drug effectsCells, CulturedImmunohistochemistryJanus Kinase 2/antagonists & inhibitorsJanus Kinase 2/geneticsJanus Kinase 2/metabolismJanus Kinase 3/antagonists & inhibitorsJanus Kinase 3/geneticsJanus Kinase 3/metabolism*MiceNeurogenesis/drug effectsNeurogenesis/geneticsNeurons/cytology*Neurons/drug effectsNeurons/metabolism*Quinazolines/pharmacologyRNA, Small Interfering/geneticsReverse Transcriptase Polymerase Chain ReactionStem Cells/cytology*Stem Cells/drug effectsStem Cells/metabolism*Tyrphostins/pharmacology
DOI
10.1002/stem.511
PMID
20979137
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
AJOU Authors
우, 현구정, 이숙이, 수환문, 창현서, 해영백, 은주
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