Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling

John M. Perry, Omid F. Harandi, Prashanth Porayette, Shailaja Hegde, Arun K. Kannan, Robert F. Paulson

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The production of mature cells necessi- tates that lineage-committed progenitor cells be constantly generated from multi- potential progenitors. In addition, the abil- ity to respond rapidly to physiologic stresses requires that the signals that regulate the maintenance of progenitor populations be coordinated with the sig- nals that promote differentiation of pro- genitors. Here we examine the signals that are necessary for the maintenance of the BMP4-dependent stress erythropoi- esis pathway. Our previous work demon- strated that BMP4, stem cell factor, and hypoxia act in concert to promote the expansion of a specialized population of stress erythroid progenitors in the spleen during the recovery from acute anemia. Our analysis shows that acute anemia leads to an almost complete mobilization of BMP4-responsive stress erythroid burst-forming units; therefore, new stress progenitors must be recruited to the spleen to replenish this system. We show that bone marrow cells can home to the spleen and, in response to a signal in the spleen microenvironment, Hedgehog, they develop into BMP4-responsive stress progenitors. Hedgehog induces the ex- pression of BMP4, and together these 2 signals are required for the development of BMP4-responsive stress progenitors. These data demonstrate that the interplay between these 2 signals is crucial for maintenance of this stress response path- way.

Original languageEnglish (US)
Pages (from-to)911-918
Number of pages8
JournalBlood
Volume113
Issue number4
DOIs
StatePublished - Jan 22 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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