C/EBPalpha initiates primitive myelopoiesis in pluripotent embryonic cells.
The molecular mechanisms that underlie the development of primitive myeloid cells in vertebrate embryos are not well understood. Here we characterize the role of cebpa during primitive myeloid cell development in Xenopus. We show that cebpa is one of the first known hematopoietic genes expressed in the embryo. Loss- and gain-of-function studies show that it is both necessary and sufficient for the development of functional myeloid cells. In addition, we show that cebpa misexpression leads to the precocious induction of myeloid cell markers in pluripotent prospective ectodermal cells, without the cells transitioning through a general mesodermal state. Finally, we use live imaging to show that cebpa-expressing cells exhibit many attributes of terminally differentiated myeloid cells, such as highly active migratory behavior, the ability to quickly and efficiently migrate toward wounds and phagocytose bacteria, and the ability to enter the circulation. Thus, C/EPBalpha is the first known single factor capable of initiating an entire myelopoiesis pathway in pluripotent cells in the embryo.
Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Yaoyao
Y
Chen
Ricardo M B
RM
Costa
Nick R
NR
Love
Ximena
X
Soto
Martin
M
Roth
Roberto
R
Paredes
Enrique
E
Amaya
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D038042:Myelopoiesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000196:embryology / Q000235:genetics; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
D022763:CCAAT-Enhancer-Binding Protein-alpha; D017931:DNA Primers; D005819:Genetic Markers; D012333:RNA, Messenger