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 language | English |
|---|---|
| Pages (from-to) | 324-334 |
| Number of pages | 11 |
| Journal | Developmental Biology |
| Volume | 311 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 15 2007 |
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Keywords
- Hematopoiesis
- Hematopoietic stem cells
- Homeobox
- Prep1
- Repopulating activity
ASJC Scopus subject areas
- Developmental Biology
Cite this
The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity. / Di Rosa, Patrizia; Villaescusa, J. Carlos; Longobardi, Elena; Iotti, Giorgio; Ferretti, Elisabetta; Diaz, Victor M.; Miccio, Annarita; Ferrari, Giuliana; Blasi, Francesco.
In: Developmental Biology, Vol. 311, No. 2, 15.11.2007, p. 324-334.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity
AU - Di Rosa, Patrizia
AU - Villaescusa, J. Carlos
AU - Longobardi, Elena
AU - Iotti, Giorgio
AU - Ferretti, Elisabetta
AU - Diaz, Victor M.
AU - Miccio, Annarita
AU - Ferrari, Giuliana
AU - Blasi, Francesco
PY - 2007/11/15
Y1 - 2007/11/15
N2 - 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.
AB - 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.
KW - Hematopoiesis
KW - Hematopoietic stem cells
KW - Homeobox
KW - Prep1
KW - Repopulating activity
UR - http://www.scopus.com/inward/record.url?scp=35748984983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35748984983&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2007.08.031
DO - 10.1016/j.ydbio.2007.08.031
M3 - Article
C2 - 17904118
AN - SCOPUS:35748984983
VL - 311
SP - 324
EP - 334
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -