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Differential Regulation of Proliferation and Differentiation in Neural Precursor Cells by the Jak Pathway
Author(s) -
Kim Yun Hee,
Chung JeeIn,
Woo Hyun Goo,
Jung YiSook,
Lee Soo Hwan,
Moon ChangHyun,
SuhKim Haeyoung,
Baik Eun Joo
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.511
Subject(s) - biology , microbiology and biotechnology , neurosphere , neural stem cell , neurogenesis , neurite , cellular differentiation , astrocyte , neurod , glial fibrillary acidic protein , stem cell , immunology , neuroscience , biochemistry , adult stem cell , central nervous system , immunohistochemistry , in vitro , gene
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. S TEM C ELLS 2010;28:1816–1828

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