| First Author | Chapple RH | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 29451493 | Mgi Jnum | J:316374 |
| Mgi Id | MGI:6834408 | Doi | 10.7554/eLife.31159 |
| Citation | Chapple RH, et al. (2018) ERalpha promotes murine hematopoietic regeneration through the Ire1alpha-mediated unfolded protein response. Elife 7:e31159 |
| abstractText | Activation of the unfolded protein response (UPR) sustains protein homeostasis (proteostasis) and plays a fundamental role in tissue maintenance and longevity of organisms. Long-range control of UPR activation has been demonstrated in invertebrates, but such mechanisms in mammals remain elusive. Here, we show that the female sex hormone estrogen regulates the UPR in hematopoietic stem cells (HSCs). Estrogen treatment increases the capacity of HSCs to regenerate the hematopoietic system upon transplantation and accelerates regeneration after irradiation. We found that estrogen signals through estrogen receptor alpha (ERalpha) expressed in hematopoietic cells to activate the protective Ire1alpha-Xbp1 branch of the UPR. Further, ERalpha-mediated activation of the Ire1alpha-Xbp1 pathway confers HSCs with resistance against proteotoxic stress and promotes regeneration. Our findings reveal a systemic mechanism through which HSC function is augmented for hematopoietic regeneration. |
