Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis
North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang I-H, Grosser T, FitzGerald GA, et al. (2007)
Nature 447(7147): 1007-1011.
Zeitschriftenaufsatz
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Autor*in
North, Trista E.;
Goessling, Wolfram;
Walkley, Carl R.;
Lengerke, Claudia;
Kopani, Kamden R.;
Lord, Allegra M.;
Weber, Gerhard J.;
Bowman, Teresa V.;
Jang, Il-Ho;
Grosser, TiloUniBi
;
FitzGerald, Garret A.;
Daley, George Q.
Alle
![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
Alle
Abstract / Bemerkung
Haematopoietic stem cell (HSC) homeostasis is tightly controlled by growth factors, signalling molecules and transcription factors. Definitive HSCs derived during embryogenesis in the aorta–gonad–mesonephros region subsequently colonize fetal and adult haematopoietic organs1,2. To identify new modulators of HSC formation and homeostasis, a panel of biologically active compounds was screened for effects on stem cell induction in the zebrafish aorta–gonad–mesonephros region. Here, we show that chemicals that enhance prostaglandin (PG) E2 synthesis increased HSC numbers, and those that block prostaglandin synthesis decreased stem cell numbers. The cyclooxygenases responsible for PGE2 synthesis were required for HSC formation. A stable derivative of PGE2 improved kidney marrow recovery following irradiation injury in the adult zebrafish. In murine embryonic stem cell differentiation assays, PGE2 caused amplification of multipotent progenitors. Furthermore, ex vivo exposure to stabilized PGE2 enhanced spleen colony forming units at day 12 post transplant and increased the frequency of long-term repopulating HSCs present in murine bone marrow after limiting dilution competitive transplantation. The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes.
Erscheinungsjahr
2007
Zeitschriftentitel
Nature
Band
447
Ausgabe
7147
Seite(n)
1007-1011
ISSN
0028-0836
eISSN
1476-4687
Page URI
https://pub.uni-bielefeld.de/record/2965341
Zitieren
North TE, Goessling W, Walkley CR, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007;447(7147):1007-1011.
North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., Weber, G. J., et al. (2007). Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 447(7147), 1007-1011. https://doi.org/10.1038/nature05883
North, Trista E., Goessling, Wolfram, Walkley, Carl R., Lengerke, Claudia, Kopani, Kamden R., Lord, Allegra M., Weber, Gerhard J., et al. 2007. “Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis”. Nature 447 (7147): 1007-1011.
North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., Weber, G. J., Bowman, T. V., Jang, I. - H., Grosser, T., et al. (2007). Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447, 1007-1011.
North, T.E., et al., 2007. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 447(7147), p 1007-1011.
T.E. North, et al., “Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis”, Nature, vol. 447, 2007, pp. 1007-1011.
North, T.E., Goessling, W., Walkley, C.R., Lengerke, C., Kopani, K.R., Lord, A.M., Weber, G.J., Bowman, T.V., Jang, I.-H., Grosser, T., FitzGerald, G.A., Daley, G.Q., Orkin, S.H., Zon, L.I.: Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 447, 1007-1011 (2007).
North, Trista E., Goessling, Wolfram, Walkley, Carl R., Lengerke, Claudia, Kopani, Kamden R., Lord, Allegra M., Weber, Gerhard J., Bowman, Teresa V., Jang, Il-Ho, Grosser, Tilo, FitzGerald, Garret A., Daley, George Q., Orkin, Stuart H., and Zon, Leonard I. “Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis”. Nature 447.7147 (2007): 1007-1011.
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