2021 Fiscal Year Research-status Report
Pathologic hematopoietic stem cell determines co-morbid symptoms in autism
| Project/Area Number |
19K16529
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Lin ChiaWen 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (20730253)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | autism / immune dysregulation / single-cell RNA seq / EHT / epigenetics / microbiome dysbiosis / HDAC1 |
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| Outline of Annual Research Achievements |
We hypothesize a common etiology within progenitors of different types underlying widespread immune dysregulation in autism. By sc-RNA seq, we traced the origin of immune dysregulation back to yolk sac (YS) and aorta-gonad-mesonephros (AGM). A shared mechanism of HDAC1-mediated transcriptional repression underlies the widespread dysregulation. Furthermore, dysregulated immunity can determine gut dysbiosis profiles in autistic mice. This study solves the long-time puzzle in autism field and hint epigenetic disturbance as a common etiology among autism models of environmental risk factors.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
It took around 6 months to find the journal suitable for this study. When shifting to journal with specific interests to psychiatric disorders, we spent a relative short time to finish the revision and got accepted.
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| Strategy for Future Research Activity |
With the single-cell resolution atlas of definitive hematopoiesis, it becomes possible to specify the pathologic mechanism at molecular levels. However, the more upstream regulation driving the epigenetic machinary remains elusive in BTBR mice. By examing the sc-RNA seq data, the decreased DEGs were significantly enriched in signaling pathways of cellular responses to stress and infection, showing an analogy to the process of hijacking host machinery during virus invasion. These changes may reflect the observation of high expression of endogenous retrovirus (ERV), the remnants of retroviral infection, in BTBR mice and hint at the source of disturbed epigenetic regulation. We will next investigate the role of ERV in host genome evolution and ASD susceptibility.
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[Journal Article] A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model2022
Author(s)
Chia-Wen Lin, Dian E Septyaningtrias, Hsu-Wen Chao , Mikiko Konda, Koji Atarashi, Kozue Takeshita, Kota Tamada, Jun Nomura, Yohei Sasagawa, Kaori Tanaka, Itoshi Nikaido, Kenya Honda, Thomas J McHugh, Toru Takumi
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Journal Title
Molelular Psychiatry
Volume: 27
Pages: 3343-3354
DOI
Peer Reviewed / Open Access
