2022 Fiscal Year Annual Research Report

Pathologic hematopoietic stem cell determines co-morbid symptoms in autism

Research Project

Project/Area Number	19K16529
Research Institution	Institute of Physical and Chemical Research
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, 客員研究員 (20730253)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	autism / immune dysregulation / single-cell RNA seq / epigenetics / endogenous retrovirus / copy number variation / gut dysbiosis
Outline of Annual Research Achievements	The research results of this grant were published to reveal the mechanism of immune dysregulation on autism etiology. By tracking the origin of immune dysregulation back to embryonic stage in specific cell types, we found an altered HDAC1 activity affects the definitive hematopoiesis in yolk sac and AGM in an autism model strain (BTBR), which therefore affects the development of microglia and hematopoietic stem cells and subsequently leads to brain inflammation and skewed immune cell profiles. We published another paper to show active ERV also manipulate the transcriptional profiles of BTBR during development. Active ERV also accelerate CNV formation in the genome, therefore, providning provde new insights to how the ancient viral infection affects autism susceptibility.