Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Smad7 promotes self-renewal of hematopoietic stem cells in vivo.

Blank Savukinas, Ulrika LU ; Karlsson, Göran LU ; Moody, Jennifer LU ; Utsugisawa, Taiju LU ; Magnusson, Mattias LU ; Singbrant, Sofie LU ; Larsson, Jonas LU and Karlsson, Stefan LU orcid (2006) In Blood 108(13). p.4246-4254
Abstract
The Smad-signaling pathway downstream of the transforming growth factor–beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid... (More)
The Smad-signaling pathway downstream of the transforming growth factor–beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad-signaling cascade in Smad7-overexpressing cells. Taken together, these data reveal an important and previously unappreciated role for the Smad-signaling pathway in the regulation of self-renewal of HSCs in vivo. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
108
issue
13
pages
4246 - 4254
publisher
American Society of Hematology
external identifiers
  • wos:000242675300048
  • scopus:33845482880
  • pmid:16917010
ISSN
1528-0020
DOI
10.1182/blood-2006-02-005611
language
English
LU publication?
yes
id
196a2b13-66cb-4137-a704-06b0adefa798 (old id 160059)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16917010&dopt=Abstract
date added to LUP
2016-04-01 12:19:07
date last changed
2021-08-11 04:25:49
@article{196a2b13-66cb-4137-a704-06b0adefa798,
  abstract     = {The Smad-signaling pathway downstream of the transforming growth factor–beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad-signaling cascade in Smad7-overexpressing cells. Taken together, these data reveal an important and previously unappreciated role for the Smad-signaling pathway in the regulation of self-renewal of HSCs in vivo.},
  author       = {Blank Savukinas, Ulrika and Karlsson, Göran and Moody, Jennifer and Utsugisawa, Taiju and Magnusson, Mattias and Singbrant, Sofie and Larsson, Jonas and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  number       = {13},
  pages        = {4246--4254},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Smad7 promotes self-renewal of hematopoietic stem cells in vivo.},
  url          = {http://dx.doi.org/10.1182/blood-2006-02-005611},
  doi          = {10.1182/blood-2006-02-005611},
  volume       = {108},
  year         = {2006},
}