2026-09-23 韓国基礎科学研究院（IBS）
脊髄損傷後に瘢痕を形成する反応性アストロサイトを、機能的なニューロンへ直接変換する遺伝子導入システム「TRANsCre-DIONE」を、基礎科学研究院（IBS）と延世大学医学部の研究チームが開発した。GFAPと炎症関連タンパク質Lcn2の双方を利用した分子スイッチにより、損傷部位の反応性アストロサイトでNeurog2を発現させ、神経細胞へのリプログラミングを誘導する。マウスでは標識細胞の87％が神経細胞マーカーを示し、電気生理学的にも神経インパルスの発生・他ニューロンからの入力を確認。処置したマウス・ラットでは運動機能が改善し、変換されたニューロンを一時的に抑制すると回復した運動機能の一部が失われたことから、新生ニューロンが機能回復に寄与したと考えられる。霊長類では脳を用いた実験で神経細胞への変換可能性も示されたが、脊髄損傷の治療効果は検証されていない。臨床応用には安全性、標的選択性、長期的な神経回路への影響などの検証が必要である。
Figure 1. Turning scar-forming cells into neurons after spinal cord injury
(A) Illustration of the treatment strategy.
(B) Treatment with TRANsCre-DIONE/Neurog2 resulted in partial recovery up to movement score 3.88/9, while untreated mice remained in near complete paralysis with movement score of below 1/9. Normal mice had reference movement score 9/9.
(C) Left: before injury, Midde two: injured control, Right: injury healed using TRANsCre-DIONE/Neurog2.
＜関連情報＞
- https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do?nttId=27047&pageIndex=1&searchCnd=&searchWrd=#toggle
- https://www.nature.com/articles/s12276-026-01815-y
TRANsCre-DIONEは、瘢痕形成能を持つ反応性アストロサイトを機能的な運動ニューロンへと分化転換させる TRANsCre-DIONE transdifferentiates scar-forming reactive astrocytes into functional motor neurons
Heeyoung An, Hye-Lan Lee, Doo-Wan Cho, Jinpyo Hong, Hye Yeong Lee, Jung Moo Lee, SunYeong Choi, In-Young Hwang, Junsung Woo, Jaekwang Lee, MinGu Park, Young-Su Yang, Su-Cheol Han, Yoon Ha & C. Justin Lee
Experimental & Molecular Medicine Published:11 September 2026
DOI:https://doi.org/10.1038/s12276-026-01815-y
Abstract
In spinal cord injury (SCI), the scar-forming reactive astrocytes with upregulated glial fibrillary acidic protein (GFAP) proliferate aberrantly near the injury site, representing a potential cellular source for transdifferentiation into neurons to replenish dead neurons. However, the conventional use of GFAP promoter to target reactive astrocytes has two inherent problems: inadvertent conversion of normal astrocytes and low efficiency due to progressive weakening of promoter activity during transdifferentiation. Here, we present TRANsCre-DIONE, a dual-promoter split-Cre system combining GFAP and Lcn2 regulatory elements with Cre-dependent Neurog2 expression under the EF1α promoter, enabling selective targeting of scar-forming reactive astrocytes. This approach achieved 87% conversion efficiency and 96% specificity in vivo. After SCI, TRANsCre-DIONE caused transdifferentiation into Isl1-positive and ChAT-positive motor neurons, reduced astrogliosis, enhanced regeneration in surrounding cells, and a significant motor recovery. These findings suggest that TRANsCre-DIONE enables efficient and selective astrocyte-to-neuron conversion and represents a promising strategy for SCI repair.
