PT  - JOURNAL ARTICLE
AU  - Julianne N.P. Smith
AU  - Brittany A. Cordova
AU  - Brian Richardson
AU  - Kelsey F. Christo
AU  - Jordan Campanelli
AU  - Alyssia V. Broncano
AU  - Jonathan Chen
AU  - Juyeun Lee
AU  - Scott J. Cameron
AU  - Justin D. Lathia
AU  - Wendy A. Goodman
AU  - Mark J. Cameron
AU  - Amar B. Desai
TI  - Sex-specific niche signaling contributes to sexual dimorphism following stem cell transplantation
AID  - 10.1101/2022.06.13.495897
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.13.495897
4099  - http://biorxiv.org/content/early/2022/06/16/2022.06.13.495897.short
4100  - http://biorxiv.org/content/early/2022/06/16/2022.06.13.495897.full
AB  - Hematopoietic stem cell (HSC) transplantation (HST) is a curative treatment for many hematopoietic cancers and bone marrow (BM) disorders but is currently limited by numerous complications including a lengthy recovery period, prolonged neutropenia resulting in severe infections and bleeding, and a high incidence of graft vs. host disease (GVHD). While clinical studies have demonstrated that sex mismatch, notably male recipients with female donor cells, results in increased risk of GVHD (likely due to male recipient minor histocompatibility antigens targeted by donor female T-cells 1), increased non-relapse mortality, and decreased overall survival, the mechanisms underlying sex-determinants on hematopoiesis and post-transplant recovery are not clear. In this manuscript we have identified: 1) unique expression of hematopoietic niche factors in the BM and spleens of male and female mice, 2) altered kinetics of hematopoietic reconstitution following transplantation when male vs. female BM is used as the donor cell source, 3) a sex-specific role for the recipient niche in promoting post HST recovery, and 4) a dose-dependent role for exogenous sex hormones in maintaining hematopoietic stem and progenitor cells (HSPCs). Taken together, these data demonstrate that sex-specific cellular and molecular signaling occurs during hematopoietic regeneration. Further identifying novel sex-dependent determinants of regeneration following transplantation will not only enhance understanding of steady state versus regeneration hematopoiesis but may also reveal unique (and potentially sex-specific) therapeutic targets to accelerate hematologic recovery.Key PointsMale and female mice display altered kinetics of regeneration following HST due to unique niche factors in hematopoietic compartments.Exogenous steroid sex hormones uniquely regulate the pool of hematopoietic stem and progenitor cells and may impact transplantation outcomes.Competing Interest StatementThe authors have declared no competing interest.