Reciprocal Activation of GATA-1 and PU.1 Marks Initial Specification of Hematopoietic Stem Cells into Myeloerythroid and Myelolymphoid Lineages

Yojiro Arinobu, Shin ichi Mizuno, Yong Chong, Hirokazu Shigematsu, Tadafumi Iino, Hiromi Iwasaki, Thomas Graf, Robin Mayfield, Susan Chan, Philippe Kastner, Koichi Akashi

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

A hierarchical hematopoietic development with myeloid versus lymphoid bifurcation has been proposed downstream of the multipotent progenitor (MPP) stage, based on prospective isolation of progenitors capable of generating only myeloerythroid cells (common myeloid progenitor, CMP) or only lymphocytes (common lymphoid progenitor, CLP). By utilizing GATA-1 and PU.1 transcription factor reporters, here we identified progenitor populations that are precursors for either CMPs or CLPs. Two independent populations expressing either GATA-1 or PU.1 resided within the CD34+Sca-1+c-Kit+ MPP fraction. The GATA-1+ MPP displayed potent myeloerythroid potential without giving rise to lymphocytes, whereas the PU.1+ MPP showed granulocyte/monocyte/lymphoid-restricted progenitor activity without megakaryocyte/erythroid differentiation. Furthermore, GATA-1+ and PU.1+ MPPs possessed huge expansion potential and differentiated into the original CMPs and CLPs, respectively. Thus, the reciprocal activation of GATA-1 and PU.1 primarily organizes the hematopoietic lineage fate decision to form the earliest hematopoietic branchpoint that comprises isolatable myeloerythroid and myelolymphoid progenitor populations.

Original languageEnglish
Pages (from-to)416-427
Number of pages12
JournalCell stem cell
Volume1
Issue number4
DOIs
Publication statusPublished - Oct 11 2007

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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