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Titolo:
STRINGENTLY PURIFIED HUMAN HEMATOPOIETIC PROGENITORS STEM-CELLS - ANALYSIS OF CELLULAR MOLECULAR MECHANISMS UNDERLYING EARLY HEMATOPOIESIS
Autore:
PESCHLE C; TESTA U; VALTIERI M; GABBIANELLI M; PELOSI E; MONTESORO E; SPOSI NM; FOSSATI C; CAMAGNA A; CARE A;
Indirizzi:
THOMAS JEFFERSON UNIV,T JEFFERSON CANC INST,BLUEMLE LIFE SCI BLDG,233S 10TH ST PHILADELPHIA PA 19107 IST SUPER SANITA,DEPT HEMATOL & ONCOL I-00161 ROME ITALY UNIV ROMA LA SAPIENZA,POLICLIN UMBERTO 1,MED CLIN 2 I-00185 ROME ITALY
Titolo Testata:
Stem cells
fascicolo: 5, volume: 11, anno: 1993,
pagine: 356 - 370
SICI:
1066-5099(1993)11:5<356:SPHHPS>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; BONE-MARROW CELLS; GROWTH-FACTOR RECEPTORS; HUMAN PERIPHERAL-BLOOD; UMBILICAL-CORD BLOOD; C-KIT LIGAND; GM-CSF; 5-FLUOROURACIL TREATMENT; HUMAN INTERLEUKIN; FORMING CELLS;
Keywords:
HEMATOPOIETIC STEM CELLS; HEMATOPOIETIC PROGENITORS; MOLECULAR BASIS OF HEMATOPOIESIS; CELLULAR BASIS OF HEMATOPOIESIS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
99
Recensione:
Indirizzi per estratti:
Citazione:
C. Peschle et al., "STRINGENTLY PURIFIED HUMAN HEMATOPOIETIC PROGENITORS STEM-CELLS - ANALYSIS OF CELLULAR MOLECULAR MECHANISMS UNDERLYING EARLY HEMATOPOIESIS", Stem cells, 11(5), 1993, pp. 356-370

Abstract

Analysis of the cellular/molecular basis of the early steps of hematopoietic proliferation and differentiation is hindered by the rarity ofhematopoietic progenitors and stem cells (HP/HSC). The intensive efforts devoted to the development of purification methods for early HP and HSC, although initially largely unsuccessful, have recently provideda high level of HP/HSC yield and/or recovery. The methodology developed by our group, recently improved, provides not only virtually complete purification, but also abundant recovery of early HP/HSC such as colony forming units granulocyte/erythroid/macrophage/megakaryocyte (CFU-GEMM), burst forming units erythroid (BFU-E), CFU granulocyte/macrophage (CFU-GM)/CFU blast cells (CFU-B), and long-term culture initiatingcells (LTC-IC) from adult peripheral and cord blood (CB). We have also developed a serum-free liquid suspension culture for unilineage erythroid (E), granulocytic (G) or monocytic (M) differentiation of stringently purified HP/HSC. These culture systems allow sequential collection and cellular/molecular analysis of discrete populations of hematopoietic cells at a homogenous stage of differentiation specifically along a unilineage pathway. These experimental tools have been utilized toinvestigate cellular/molecular mechanisms underlying early hematopoiesis. The transcription factor (TF) GATA-1 is considered to be the ''master'' gene of erythropoiesis. In highly purified HP/HSC undergoing E or GM differentiation, GATA-1 expression is characterized initially byproliferation-dependent activation and at later stages by sustained expression in the E pathway and suppression in the GM pathway. Hypothetically, similar on/off switches of lineage-restricted TF may underlie the binary fate decisions of early HP differentiation. The expression and modulation of hematopoietic growth factor receptors (HGFR) in early hematopoiesis have been extensively analyzed. The results suggest a model of transactivation cascade for HGFR such as interleukin 6 receptor (IL-6R), IL-3R, GM colony stimulating factor receptor (GM-CSFR), and erythropoietin receptor (EpR), whereby each HGF upmodulates the R(s)for distal-acting HGF(s). Finally, we have investigated the effect ofHGF on reactivation of hemoglobin F (HbF) in clonogenic or liquid suspension serum-free culture of purified adult HP. The results suggest that c-kit ligand (KL) plays a key role in the reactivation of HbF synthesis in adult life, and IL-3/GM-CSF potentiate this effect at low KL level. The KL-induced HbF reactivation is seemingly related to an enhanced proliferation of early E progenitors in their differentiation pathway.

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Documento generato il 20/09/20 alle ore 10:43:58