Organ-injury-induced reactivation of hemangioblastic precursor cells

Leukemia. 2008 Jan;22(1):103-13. doi: 10.1038/sj.leu.2404941. Epub 2007 Sep 27.

Abstract

Early in mammalian development, the stem cell leukemia (SCL/TAL1) gene and its distinct 3' enhancer (SCL 3'En) specify bipotential progenitor cells that give rise to blood and endothelium, thus termed hemangioblasts. We have previously detected a minor population of SCL (+) cells in the postnatal kidney. Here, we demonstrate that cells expressing the SCL 3'En in the adult kidney are comprised of CD45+CD31- hematopoietic cells, CD45-CD31+ endothelial cells and CD45-CD31- interstitial cells. Creation of bone marrow chimeras of SCL 3'En transgenic mice into wild-type hosts shows that all three types of SCL 3'En-expressing cells in the adult kidney can originate from the bone marrow. Ischemia/reperfusion injury to the adult kidney of SCL 3'En transgenic mice results in the intrarenal elevation of SCL and FLK1 mRNA levels and of cells expressing hem-endothelial progenitor markers (CD45, CD34, c-Kit and FLK1). Furthermore, analysis of SCL 3'En in the ischemic kidneys reveals an increase in the abundance of SCL 3'En-expressing cells, predominantly within the CD45 (+) hematopoietic fraction and to a lesser extent in the CD45 (-) fraction. Our results suggest organ-injury-induced reactivation of bone marrow-derived hemangioblasts and possible local angioblastic progenitors expressing SCL and SCL 3'En.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, CD34 / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cells / metabolism*
  • Kidney Diseases / metabolism*
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy
  • Pregnancy, Animal
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Reperfusion Injury / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Antigens, CD34
  • Basic Helix-Loop-Helix Transcription Factors
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2
  • Leukocyte Common Antigens