김혜성 (Columbia University, 단국대학교) | 한빛사논문 > 한빛사

한빛사논문

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Columbia University, 단국대학교

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Adv. Sci., Mar 28 2024, | https://doi.org/10.1002/advs.202400847 Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids

Hye Sung Kim ^{1 2 3 4 †}, Yang Xiao ^{1 †}, Xuejing Chen ^{1 5}, Siyu He ¹, Jongwon Im ¹, Moshe J Willner ¹, Michael O Finlayson ⁶, Cong Xu ¹, Huixiang Zhu ⁷, Se Joon Choi ^{7 8}, Eugene V Mosharov ^{7 8}, Hae-Won Kim ^{2 3 4}, Bin Xu^{7 *}, Kam W Leong ^{1 9 *}

¹Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.

²Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.

³Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea.

⁴Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.

⁵Department of Physics, Tsinghua University, Beijing, 100084, China.

⁶Single Cell Analysis Core, JP Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY, 10032, USA.

⁷Department of Psychiatry, Columbia University Medical Center, New York, NY, 10032, USA.

⁸Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032, USA.

⁹Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA.

^†H.S.K. and Y.X. contributed equally to this work.
^*Corresponding authors: correspondence to Bin Xu or Kam W Leong

Abstract

Understanding the impact of long-term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency. However, this has been limited by human brain inaccessibility and cross-species differences in animal models. Here, a human midbrain model is established that uses hiPSC-derived midbrain organoids to assess cell-type-specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single-cell mRNA sequencing of 25,510 cells from organoids in different treatment groups reveals that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single-cell level.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-01)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오소재

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