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The stem cell regulator PEDF is dispensable for maintenance and function of hematopoietic stem cells

Rörby, Emma LU ; Billing, Matilda LU ; Dahl, Maria LU ; Warsi, Sarah LU ; Andradottir, Silja LU ; Miharada, Kenichi LU ; Siva, Kavitha LU ; Jönsson, Jan-Ingvar; Blank, Ulrika and Karlsson, Göran LU , et al. (2017) In Scientific Reports 7.
Abstract

Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation... (More)

Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation setting. Additionally, PEDF-deficient cells exhibit unaltered lineage distribution upon serial transplantations. When human cord blood stem and progenitor cells were cultured in media supplemented with recombinant PEDF they did not show changes in growth potential. Taken together, we report that PEDF is not a critical regulatory factor for HSC function during regeneration in vivo or growth of human stem/progenitor cells in vitro.

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Journal Article
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Scientific Reports
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:85028642225
  • wos:000408781000030
ISSN
2045-2322
DOI
10.1038/s41598-017-09452-2
language
English
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yes
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6b0c2cb7-f361-44fb-8060-fb5338b6af3e
date added to LUP
2017-09-07 14:38:49
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2018-01-09 13:05:29
@article{6b0c2cb7-f361-44fb-8060-fb5338b6af3e,
  abstract     = {<p>Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation setting. Additionally, PEDF-deficient cells exhibit unaltered lineage distribution upon serial transplantations. When human cord blood stem and progenitor cells were cultured in media supplemented with recombinant PEDF they did not show changes in growth potential. Taken together, we report that PEDF is not a critical regulatory factor for HSC function during regeneration in vivo or growth of human stem/progenitor cells in vitro.</p>},
  articleno    = {10134},
  author       = {Rörby, Emma and Billing, Matilda and Dahl, Maria and Warsi, Sarah and Andradottir, Silja and Miharada, Kenichi and Siva, Kavitha and Jönsson, Jan-Ingvar and Blank, Ulrika and Karlsson, Göran and Karlsson, Stefan},
  issn         = {2045-2322},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {08},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {The stem cell regulator PEDF is dispensable for maintenance and function of hematopoietic stem cells},
  url          = {http://dx.doi.org/10.1038/s41598-017-09452-2},
  volume       = {7},
  year         = {2017},
}