TY - JOUR
T1 - Reciprocal Activation of GATA-1 and PU.1 Marks Initial Specification of Hematopoietic Stem Cells into Myeloerythroid and Myelolymphoid Lineages
AU - Arinobu, Yojiro
AU - Mizuno, Shin ichi
AU - Chong, Yong
AU - Shigematsu, Hirokazu
AU - Iino, Tadafumi
AU - Iwasaki, Hiromi
AU - Graf, Thomas
AU - Mayfield, Robin
AU - Chan, Susan
AU - Kastner, Philippe
AU - Akashi, Koichi
N1 - Funding Information:
This work was supported in part by grants from the National Institutes of Health (NIH) (DK050654, DK061320, and CA072009) and from a Special Research Grant-In-Aid for Development of Characteristic Education from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. We also thank D. Scadden for helping us by preserving the GATA-1-GFP reporter mouse strain.
PY - 2007/10/11
Y1 - 2007/10/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2007.07.004
DO - 10.1016/j.stem.2007.07.004
M3 - Article
C2 - 18371378
AN - SCOPUS:34848883146
SN - 1934-5909
VL - 1
SP - 416
EP - 427
JO - Cell stem cell
JF - Cell stem cell
IS - 4
ER -