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Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture.

Singbrant, Sofie LU ; Karlsson, Göran LU ; Ehinger, Mats LU ; Olsson, Karin LU ; Jaako, Pekka LU ; Miharada, Kenichi LU ; Stadtfeld, Matthias; Graf, Thomas and Karlsson, Stefan LU (2010) In Blood 115. p.4689-4698
Abstract
Numerous publications have described the importance of Bone Morphogenetic Protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies, since conventional disruption of components of the BMP signaling pathway result in early death of the embryo. By targeting both Smad1 and Smad5, we have generated a double knockout mouse with complete disruption of canonical BMP signaling. Interestingly, concurrent deletion of Smad1 and Smad5 results in death due to extra-hematopoietic pathological changes in the colon. However, Smad1/5 deficient bone marrow (BM) cells can compete... (More)
Numerous publications have described the importance of Bone Morphogenetic Protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies, since conventional disruption of components of the BMP signaling pathway result in early death of the embryo. By targeting both Smad1 and Smad5, we have generated a double knockout mouse with complete disruption of canonical BMP signaling. Interestingly, concurrent deletion of Smad1 and Smad5 results in death due to extra-hematopoietic pathological changes in the colon. However, Smad1/5 deficient bone marrow (BM) cells can compete normally with wild-type cells and display unaffected self-renewal and differentiation capacity when transplanted into lethally irradiated recipients. Moreover, although BMP receptor expression is increased in fetal liver, fetal liver cells deficient in both Smad1 and Smad5 remain competent to long-term reconstitute lethally irradiated recipients in a multi-lineage manner. In conclusion, canonical BMP signaling is not required to maintain either adult or fetal liver hematopoiesis, despite its crucial role in the initial patterning of hematopoiesis in early embryonic development. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
115
pages
4689 - 4698
publisher
American Society of Hematology
external identifiers
  • wos:000278635900015
  • pmid:20371744
  • scopus:77954704813
ISSN
1528-0020
DOI
10.1182/blood-2009-05-220988
language
English
LU publication?
yes
id
351f0522-3f86-4465-950a-76ee8deca90d (old id 1595538)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20371744?dopt=Abstract
date added to LUP
2010-05-04 10:37:51
date last changed
2018-05-29 11:34:10
@article{351f0522-3f86-4465-950a-76ee8deca90d,
  abstract     = {Numerous publications have described the importance of Bone Morphogenetic Protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies, since conventional disruption of components of the BMP signaling pathway result in early death of the embryo. By targeting both Smad1 and Smad5, we have generated a double knockout mouse with complete disruption of canonical BMP signaling. Interestingly, concurrent deletion of Smad1 and Smad5 results in death due to extra-hematopoietic pathological changes in the colon. However, Smad1/5 deficient bone marrow (BM) cells can compete normally with wild-type cells and display unaffected self-renewal and differentiation capacity when transplanted into lethally irradiated recipients. Moreover, although BMP receptor expression is increased in fetal liver, fetal liver cells deficient in both Smad1 and Smad5 remain competent to long-term reconstitute lethally irradiated recipients in a multi-lineage manner. In conclusion, canonical BMP signaling is not required to maintain either adult or fetal liver hematopoiesis, despite its crucial role in the initial patterning of hematopoiesis in early embryonic development.},
  author       = {Singbrant, Sofie and Karlsson, Göran and Ehinger, Mats and Olsson, Karin and Jaako, Pekka and Miharada, Kenichi and Stadtfeld, Matthias and Graf, Thomas and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  pages        = {4689--4698},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture.},
  url          = {http://dx.doi.org/10.1182/blood-2009-05-220988},
  volume       = {115},
  year         = {2010},
}