Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum stress.

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Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum stress. / Miharada, Kenichi; Sigurdsson, Valgardur; Karlsson, Stefan.

I: Cell Reports, Vol. 7, Nr. 5, 2014, s. 1381-1392.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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TY - JOUR

T1 - Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum stress.

AU - Miharada, Kenichi

AU - Sigurdsson, Valgardur

AU - Karlsson, Stefan

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2014.04.056

DO - 10.1016/j.celrep.2014.04.056

M3 - Article

VL - 7

SP - 1381

EP - 1392

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -