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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)
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author
organization
publishing date
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
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
2014-07-04 12:02:44
date last changed
2017-10-22 04:23:34
@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          = {http://dx.doi.org/10.1016/j.celrep.2014.04.056},
  volume       = {7},
  year         = {2014},
}