| 研究実績の概要 |
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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| 今後の研究の推進方策 |
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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