title: Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages.
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.
authors: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors: Yojiro
authors: Y
authors: Arinobu
authors: Shin-ichi
authors: S
authors: Mizuno
authors: Yong
authors: Y
authors: Chong
authors: Hirokazu
authors: H
authors: Shigematsu
authors: Tadafumi
authors: T
authors: Iino
authors: Hiromi
authors: H
authors: Iwasaki
authors: Thomas
authors: T
authors: Graf
authors: Robin
authors: R
authors: Mayfield
authors: Susan
authors: S
authors: Chan
authors: Philippe
authors: P
authors: Kastner
authors: Koichi
authors: K
authors: Akashi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D002454:Cell Differentiation; D019070:Cell Lineage; D015672:Erythroid Precursor Cells / Q000166:cytology*; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology; D054503:Lymphoid Progenitor Cells / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D039902:Multipotent Stem Cells / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D018952:Antigens, CD34; D000067696:Ataxin-1; D000067528:Ataxins; D050982:GATA1 Transcription Factor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C000593750:Atxn1 protein, mouse