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A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic progenitor cells.

Billing, Matilda LU ; Rörby, Emma LU ; May, Gillian; Tipping, Alex J; Soneji, Shamit LU ; Brown, John; Salminen, Marjo; Karlsson, Göran LU ; Enver, Tariq and Karlsson, Stefan LU (2016) In Experimental Hematology 44(5). p.399-409
Abstract
Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell (HSC) function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFβ response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFβ signaling effector molecule p57 was found to be upregulated as a secondary response to TGFβ. We observed Gata2 binding upstream of the p57 genomic... (More)
Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell (HSC) function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFβ response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFβ signaling effector molecule p57 was found to be upregulated as a secondary response to TGFβ. We observed Gata2 binding upstream of the p57 genomic locus, and importantly loss of Gata2 abolished TGFβ-stimulated induction of p57 as well as the resulting growth arrest of hematopoietic progenitors. Our results connect key molecules involved in HSC self-renewal and reveal a functionally relevant network regulating proliferation of primitive hematopoietic cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Hematology
volume
44
issue
5
pages
399 - 409
publisher
Elsevier
external identifiers
  • pmid:26876150
  • scopus:84962052965
  • wos:000375025300011
ISSN
1873-2399
DOI
10.1016/j.exphem.2016.02.001
language
English
LU publication?
yes
id
a1b2ad63-6f89-4165-993c-3e0a73dd4879 (old id 8825487)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26876150?dopt=Abstract
date added to LUP
2016-03-04 11:06:25
date last changed
2017-08-21 10:23:37
@article{a1b2ad63-6f89-4165-993c-3e0a73dd4879,
  abstract     = {Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell (HSC) function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFβ response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFβ signaling effector molecule p57 was found to be upregulated as a secondary response to TGFβ. We observed Gata2 binding upstream of the p57 genomic locus, and importantly loss of Gata2 abolished TGFβ-stimulated induction of p57 as well as the resulting growth arrest of hematopoietic progenitors. Our results connect key molecules involved in HSC self-renewal and reveal a functionally relevant network regulating proliferation of primitive hematopoietic cells.},
  author       = {Billing, Matilda and Rörby, Emma and May, Gillian and Tipping, Alex J and Soneji, Shamit and Brown, John and Salminen, Marjo and Karlsson, Göran and Enver, Tariq and Karlsson, Stefan},
  issn         = {1873-2399},
  language     = {eng},
  month        = {02},
  number       = {5},
  pages        = {399--409},
  publisher    = {Elsevier},
  series       = {Experimental Hematology},
  title        = {A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic progenitor cells.},
  url          = {http://dx.doi.org/10.1016/j.exphem.2016.02.001},
  volume       = {44},
  year         = {2016},
}