TY - JOUR TI - ERα promotes murine hematopoietic regeneration through the Ire1α-mediated unfolded protein response AU - Chapple, Richard H AU - Hu, Tianyuan AU - Tseng, Yu-Jung AU - Liu, Lu AU - Kitano, Ayumi AU - Luu, Victor AU - Hoegenauer, Kevin A AU - Iwawaki, Takao AU - Li, Qing AU - Nakada, Daisuke A2 - Lo Celso, Cristina VL - 7 PY - 2018 DA - 2018/02/16 SP - e31159 C1 - eLife 2018;7:e31159 DO - 10.7554/eLife.31159 UR - https://doi.org/10.7554/eLife.31159 AB - 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 α (ERα) expressed in hematopoietic cells to activate the protective Ire1α-Xbp1 branch of the UPR. Further, ERα-mediated activation of the Ire1α-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. KW - Hematopoietic stem cells KW - unfolded protein response KW - estrogen KW - regeneration KW - irradiation KW - Ire1 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -