The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity

Patrizia Di Rosa, J. Carlos Villaescusa, Elena Longobardi, Giorgio Iotti, Elisabetta Ferretti, Victor M. Diaz, Annarita Miccio, Giuliana Ferrari, Francesco Blasi

Research output: Contribution to journalArticlepeer-review

Abstract

Most of the hypomorphic Prep1i/i embryos (expressing 3-10% of the Prep1 protein), die between E17.5 and P0, with profound anemia, eye malformations and angiogenic anomalies [Ferretti, E., Villaescusa, J.C., Di Rosa, P., Fernandez-Diaz, L.-C., Longobardi, E., Mazzieri, R., Miccio, A., Micali, N., Selleri, L., Ferrari G., Blasi, F. (2006). Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype. Mol. Cell. Biol. 26, 5650-5662]. We now report on the hematopoietic phenotype of these embryos. Prep1i/i fetal livers (FL) are hypoplastic, produce less common myeloid progenitors colonies (CFU-GEMM) in cytokine-supplemented methylcellulose and have an increased number of B-cells precursors that differentiate poorly. Prep1i/i FL is able to protect lethally irradiated mice only at high cell doses but the few protected mice show major anomalies in all hematopoietic lineages in both bone marrow (BM) and peripheral organs. Prep1i/i FL cells compete inefficiently with wild type bone marrow in competitive repopulation experiments, suggesting that the major defect lies in long-term repopulating hematopoietic stem cells (LTR-HSC). Indeed, wt embryonic expression of Prep1 in the aorta-gonad-mesonephros (AGM) region, fetal liver (FL), cKit+Sca1+Lin-AA4.1+ (KSLA) cells and B-lymphocytes precursors agrees with the observed phenotype. We therefore conclude that Prep1 is required for a correct and complete hematopoiesis.

Original languageEnglish
Pages (from-to)324-334
Number of pages11
JournalDevelopmental Biology
Volume311
Issue number2
DOIs
Publication statusPublished - Nov 15 2007

Keywords

  • Hematopoiesis
  • Hematopoietic stem cells
  • Homeobox
  • Prep1
  • Repopulating activity

ASJC Scopus subject areas

  • Developmental Biology

Fingerprint Dive into the research topics of 'The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity'. Together they form a unique fingerprint.

Cite this