SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia

Jun Takouda; Sayako Katada; Takuya Imamura; Tsukasa Sanosaka; Kinichi Nakashima

doi:10.1002/prp2.749

journal article Open Access Oct 22, 2021

SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia

Jun Takouda Sayako Katada

Takuya Imamura

Tsukasa Sanosaka Kinichi Nakashima

Pharmacology Research & Perspectives Vol. 9 No. 6 · Wiley

View at Publisher Save 10.1002/prp2.749

Abstract

AbstractThe brain consists of three major cell types: neurons and two glial cell types (astrocytes and oligodendrocytes). Although they are generated from common multipotent neural stem/precursor cells (NS/PCs), embryonic NS/PCs cannot generate all of the cell types at the beginning of brain development. NS/PCs first undergo extensive self‐renewal to expand their pools, and then acquire the potential to produce neurons, followed by glial cells. Astrocytes are the most frequently found cell type in the central nervous system (CNS), and play important roles in brain development and functions. Although it has been shown that nuclear factor IA (Nfia) is a pivotal transcription factor for conferring gliogenic potential on neurogenic NS/PCs by sequestering DNA methyltransferase 1 (Dnmt1) from astrocyte‐specific genes, direct targets of Nfia that participate in astrocytic differentiation have yet to be completely identified. Here we show that SRY‐box transcription factor 8 (Sox8) is a direct target gene of Nfia at the initiation of the gliogenic phase. We found that expression of Sox8 augmented leukemia inhibitory factor (LIF)‐induced astrocytic differentiation, while Sox8 knockdown inhibited Nfia‐enhanced astrocytic differentiation of NS/PCs. In contrast to Nfia, Sox8 did not induce DNA demethylation of an astrocyte‐specific marker gene, glial fibrillary acidic protein (Gfap), but instead associated with LIF downstream transcription factor STAT3 through transcriptional coactivator p300, explaining how Sox8 expression further facilitated LIF‐induced Gfap expression. Taken together, these results suggest that Sox8 is a crucial Nfia downstream transcription factor for the astrocytic differentiation of NS/PCs in the developing brain.

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Details

Published: Oct 22, 2021
Vol/Issue: 9(6)
License: View

Authors

J

Jun Takouda

Department of Stem Cell Biology and Medicine Graduate School of Medical Sciences Kyushu University Fukuoka Japan

S

Sayako Katada

Department of Stem Cell Biology and Medicine Graduate School of Medical Sciences Kyushu University Fukuoka Japan

T

Takuya Imamura

Department of Stem Cell Biology and Medicine Graduate School of Medical Sciences Kyushu University Fukuoka Japan; Program of Biomedical Science Graduate School of Integrated Sciences for Life Hiroshima University Higashi‐Hiroshima Japan

T

Tsukasa Sanosaka

Department of Physiology Keio University School of Medicine Tokyo Japan

K

Kinichi Nakashima

Department of Stem Cell Biology and Medicine Graduate School of Medical Sciences Kyushu University Fukuoka Japan

Funding

Japan Society for the Promotion of Science Award: JP16H06527

Cite This Article

Jun Takouda, Sayako Katada, Takuya Imamura, et al. (2021). SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia. Pharmacology Research & Perspectives, 9(6). https://doi.org/10.1002/prp2.749

SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia

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