2026-08-25 東北大学
図1. 若齢造血幹細胞と加齢造血幹細胞
＜関連情報＞
- https://www.tohoku.ac.jp/japanese/2026/08/press20260825-01-pbx1.html
- https://www.science.org/doi/10.1126/sciadv.aeb1346
Geneformerを用いたマルチオミクス統合により、Pbx1が造血幹細胞老化のネットワークハブであることが同定された Geneformer-guided multiomics integration identifies Pbx1 as a network hub of hematopoietic stem cell aging
Hiroshi Kobayashi, Shintaro Watanuki, Yusuke Shiozawa, Motohiko Oshima, […] , and Keiyo Takubo
Science Advances Published:21 Aug 2026
DOI:https://doi.org/10.1126/sciadv.aeb1346
Abstract
Hematopoietic stem cells (HSCs) constitute an organized hematopoietic system that undergoes age-related alterations, including increased platelet production and decreased erythropoiesis. The fundamental mechanisms driving these shifts remain incompletely understood. We used single-cell RNA sequencing data to show that old HSCs contain two distinct transcriptional programs: one shared with megakaryocytes and the other reflecting the most primitive HSC state. Developmental time-series profiling further suggests that the acquisition of these programs begins early in life, with the primitive module rising prenatally and megakaryocytic priming emerging after birth. Using a fine-tuned Geneformer (transformer-based deep learning model) to capture higher-order differences between young and old HSCs, coupled with transcriptomic and epigenetic profiling, as well as transcription factor screens, we identified Pbx1 as a key regulator of these age-related transcriptional and differentiation changes. Specifically, Pbx1 suppresses erythroid differentiation by repressing Gata1 expression. These findings provide insight into HSC aging and may inform approaches to modulate age-associated HSC dysfunction.
