title: High mobility group nucleosome-binding family proteins promote astrocyte differentiation of neural precursor cells.
abstract: Astrocytes are the most abundant cell type in the mammalian brain and are important for the functions of the central nervous system. Although previous studies have shown that the STAT signaling pathway or its regulators promote the generation of astrocytes from multipotent neural precursor cells (NPCs) in the developing mammalian brain, the molecular mechanisms that regulate the astrocytic fate decision have still remained largely unclear. Here, we show that the high mobility group nucleosome-binding (HMGN) family proteins, HMGN1, 2, and 3, promote astrocyte differentiation of NPCs during brain development. HMGN proteins were expressed in NPCs, Sox9(+) glial progenitors, and GFAP(+) astrocytes in perinatal and adult brains. Forced expression of either HMGN1, 2, or 3 in NPCs in cultures or in the late embryonic neocortex increased the generation of astrocytes at the expense of neurons. Conversely, knockdown of either HMGN1, 2, or 3 in NPCs suppressed astrocyte differentiation and promoted neuronal differentiation. Importantly, overexpression of HMGN proteins did not induce the phosphorylation of STAT3 or activate STAT reporter genes. In addition, HMGN family proteins did not enhance DNA demethylation and acetylation of histone H3 around the STAT-binding site of the gfap promoter. Moreover, knockdown of HMGN family proteins significantly reduced astrocyte differentiation induced by gliogenic signal ciliary neurotrophic factor, which activates the JAK-STAT pathway. Therefore, we propose that HMGN family proteins are novel chromatin regulatory factors that control astrocyte fate decision/differentiation in parallel with or downstream of the JAK-STAT pathway through modulation of the responsiveness to gliogenic signals.
authors: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan.
authors: Motoshi
authors: M
authors: Nagao
authors: Darin
authors: D
authors: Lanjakornsiripan
authors: Yasuhiro
authors: Y
authors: Itoh
authors: Yusuke
authors: Y
authors: Kishi
authors: Toru
authors: T
authors: Ogata
authors: Yukiko
authors: Y
authors: Gotoh
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D024001:HMGN Proteins / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D024001:HMGN Proteins; D050796:STAT3 Transcription Factor
keywords: Astrocytes; Chromatin; High mobility group nucleosome-binding proteins; Neural stem cells; STAT3 transcription factor