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Transforming growth factor‐β1 causes transcriptional activation of CD34 and preserves haematopoietic stem/progenitor cell activity
Author(s) -
Pierelli Luca,
Marone Maria,
Bonanno Giuseppina,
Rutella Sergio,
De Ritis Daniela,
Mancuso Salvatore,
Leone Giuseppe,
Scambia Giovanni
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03604.x
Subject(s) - haematopoiesis , progenitor cell , stem cell , microbiology and biotechnology , cd34 , biology , stem cell factor , cellular differentiation , biochemistry , gene
Summary. Stem/progenitor cells endowed with in vitro and in vivo haematopoietic activity express the surface protein CD34. Transforming growth factor β1 (TGF‐β1) is one of the soluble molecules that regulate cell cycle and differentiation of haematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has previously been shown that TGF‐β1 maintains human CD34 + haematopoietic progenitors in an undifferentiated state, independently of any cell cycle effect. Here, we have shown that TGF‐β1 upregulates the human CD34, an effect that was evident in primary stem/progenitor cells (CD34 + lin – ) both at the transcriptional and protein levels, and was not associated with any relevant effect on cell growth. The presence of TGF‐β1 influenced differentiation, maintaining primary CD34 + /Lin – in an undifferentiated state. This effect was associated with Smad activation and with a dramatic decrease in p38 phosphorylation. Moreover, blocking p38 phosphorylation by the SB202190 inhibitor increased CD34 RNA levels but did not enhance CD34 protein expression in CD34 + /Lin – cells, suggesting that modulation of multiple signalling pathways is necessary to reproduce TGF‐β1 effects. These data establish the role that TGF‐β1 has in the modulation of the CD34 stem/progenitor protein and stem/progenitor functions, providing important clues for understanding haematopoietic development and a potential tool for the modulation of human haematopoiesis.