Smad5 is dispensable for adult murine hematopoiesis.
Singbrant, Sofie LU ; Moody, Jennifer LU ; Blank Savukinas, Ulrika LU ; Karlsson, Göran LU ; Umans, Lieve ; Zwijsen, An and Karlsson, Stefan LU
(2006)
In Blood
108(12).
p.3707-3712
- Abstract
- Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre-mediated conditional knockout model. Surprisingly, analysis of induced animals revealed unperturbed cell numbers and lineage distribution in... (More)
- Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre-mediated conditional knockout model. Surprisingly, analysis of induced animals revealed unperturbed cell numbers and lineage distribution in peripheral blood (PB), bone marrow (BM), and the spleen. Furthermore, phenotypic characterization of the stem cell compartment revealed normal numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK) cells in Smad5(-/-) BM. When transplanted in a competitive fashion into lethally irradiated primary and secondary recipients, Smad5-deficient BM cells competed normally with wild-type (wt) cells, were able to provide long-term reconstitution for the hosts, and displayed normal lineage distribution. Taken together, Smad5-deficient HSCs from adult mice show unaltered differentiation, proliferation, and repopulating capacity. Therefore, in contrast to its role in embryonic hematopoiesis, Smad5 is dispensable for hematopoiesis in the adult mouse. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/160193
- author
- Singbrant, Sofie
LU
; Moody, Jennifer
LU
; Blank Savukinas, Ulrika
LU
; Karlsson, Göran
LU
; Umans, Lieve
; Zwijsen, An
and Karlsson, Stefan
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 108
- issue
- 12
- pages
- 3707 - 3712
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000242309800020
- scopus:33845245178
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2006-02-003384
- language
- English
- LU publication?
- yes
- id
- 117cf350-1418-47ee-a9b9-8d24167653e6 (old id 160193)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16896158&dopt=Abstract
- date added to LUP
- 2016-04-01 12:05:36
- date last changed
- 2022-01-26 22:40:49
@article{117cf350-1418-47ee-a9b9-8d24167653e6,
abstract = {{Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre-mediated conditional knockout model. Surprisingly, analysis of induced animals revealed unperturbed cell numbers and lineage distribution in peripheral blood (PB), bone marrow (BM), and the spleen. Furthermore, phenotypic characterization of the stem cell compartment revealed normal numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK) cells in Smad5(-/-) BM. When transplanted in a competitive fashion into lethally irradiated primary and secondary recipients, Smad5-deficient BM cells competed normally with wild-type (wt) cells, were able to provide long-term reconstitution for the hosts, and displayed normal lineage distribution. Taken together, Smad5-deficient HSCs from adult mice show unaltered differentiation, proliferation, and repopulating capacity. Therefore, in contrast to its role in embryonic hematopoiesis, Smad5 is dispensable for hematopoiesis in the adult mouse.}},
author = {{Singbrant, Sofie and Moody, Jennifer and Blank Savukinas, Ulrika and Karlsson, Göran and Umans, Lieve and Zwijsen, An and Karlsson, Stefan}},
issn = {{1528-0020}},
language = {{eng}},
number = {{12}},
pages = {{3707--3712}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Smad5 is dispensable for adult murine hematopoiesis.}},
url = {{http://dx.doi.org/10.1182/blood-2006-02-003384}},
doi = {{10.1182/blood-2006-02-003384}},
volume = {{108}},
year = {{2006}},
}