title: Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum stress.
abstract: Developmental pluripotency-associated 5 (Dppa5) is an RNA binding protein highly expressed in undifferentiated pluripotent stem cells. Here, we demonstrate that Dppa5 is a regulator of hematopoietic stem cells (HSCs) that critically governs reconstitution capacity after bone marrow transplantation. Ectopic expression of Dppa5 followed by in vitro culture robustly increased HSC reconstitution levels through suppression of endoplasmic reticulum (ER) stress and apoptosis. Remarkably, a chemical chaperone that decreases ER stress in HSCs also increases HSC engraftment. Conversely, knockdown of Dppa5 impaired the long-term reconstitution ability of HSCs due to elevated ER stress levels, suggesting that ER stress regulation is physiologically important for proper HSC function in vivo. Thus, Dppa5 represents a pivotal connection between ER stress regulation and stem cell properties in HSCs. The findings also demonstrate that protein quality control is critical for the maintenance, survival, and function of HSCs in vivo and ex vivo.
authors.affiliation: Department for Molecular Medicine and Gene Therapy, Lund Strategic Center for Stem Cell Biology, Lund University, Lund 221 84, Sweden. Electronic address: kenichi.miharada@med.lu.se.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miharada
authors.affiliation: Department for Molecular Medicine and Gene Therapy, Lund Strategic Center for Stem Cell Biology, Lund University, Lund 221 84, Sweden.
authors.forename: Valgardur
authors.initials: V
authors.lastname: Sigurdsson
authors.affiliation: Department for Molecular Medicine and Gene Therapy, Lund Strategic Center for Stem Cell Biology, Lund University, Lund 221 84, Sweden. Electronic address: stefan.karlsson@med.lu.se.
authors.forename: Stefan
authors.initials: S
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D017209:Apoptosis; D019070:Cell Lineage; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C507362:Dppa5 protein, mouse; D011506:Proteins