Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum stress.
Miharada, Kenichi LU ; Sigurdsson, Valgardur LU and Karlsson, Stefan LU
(2014)
In Cell Reports
7(5).
p.1381-1392
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4529577
- author
- Miharada, Kenichi
LU
; Sigurdsson, Valgardur
LU
and Karlsson, Stefan
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Reports
- volume
- 7
- issue
- 5
- pages
- 1381 - 1392
- publisher
- Cell Press
- external identifiers
-
- pmid:24882002
- wos:000338324200006
- scopus:84902343965
- pmid:24882002
- ISSN
- 2211-1247
- DOI
- 10.1016/j.celrep.2014.04.056
- language
- English
- LU publication?
- yes
- id
- 228c2273-120b-4350-b93f-1b1c3ffd920e (old id 4529577)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24882002?dopt=Abstract
- date added to LUP
- 2016-04-01 14:42:21
- date last changed
- 2022-04-22 04:46:19
@article{228c2273-120b-4350-b93f-1b1c3ffd920e,
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.}},
author = {{Miharada, Kenichi and Sigurdsson, Valgardur and Karlsson, Stefan}},
issn = {{2211-1247}},
language = {{eng}},
number = {{5}},
pages = {{1381--1392}},
publisher = {{Cell Press}},
series = {{Cell Reports}},
title = {{Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum stress.}},
url = {{https://lup.lub.lu.se/search/files/4120196/5268133}},
doi = {{10.1016/j.celrep.2014.04.056}},
volume = {{7}},
year = {{2014}},
}