Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a g
Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.
Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Molecular Medicine and Gene Therapy, Stem cell and red cell biology, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för molekylärmedicin och genterapi, Stem cell and red cell biology, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Molecular Medicine and Gene Therapy, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för molekylärmedicin och genterapi, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Molecular Hematology (DMH), Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för molekylär hematologi, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Molecular Hematology (DMH), Stem Cells and Leukemia, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för molekylär hematologi, Stem Cells and Leukemia, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Molecular Medicine and Gene Therapy, Stem Cells to Red Blood Cells, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för molekylärmedicin och genterapi, Stamceller till röda blodkroppar, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), StemTherapy: National Initiative on Stem Cells for Regenerative Therapy, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), StemTherapy: National Initiative on Stem Cells for Regenerative Therapy, Originator
