title: Repression of Primitive Erythroid Program Is Critical for the Initiation of Multi-Lineage Hematopoiesis in Mouse Development.
abstract: Formation of the hematopoietic cells occurs in multiple steps. The first hematopoietic cells observed during ontogeny are primitive erythrocytes, which are produced in the early yolk sac within a limited temporal window. Multi-lineage hematopoiesis, which supplies almost the entire repertoire of blood cell lineages, lags behind primitive erythropoiesis in the tissue. However, molecular mechanisms regulating sequential generation of primitive erythrocytes and multipotent hematopoietic progenitors in the yolk sac are largely unknown. In this study, the transcription factors involved in the development of hematopoietic cells were examined in purified progenitor cell populations from pluripotent stem cell cultures and from the yolk sac of developing embryos. We found that the earliest committed hematopoietic progenitors highly expressed Gata1, Scl/tal1, and Klf1 genes. Expression of these transcription factors, which is known to form a core erythroid transcriptional network, explained the prompt generation of primitive erythrocytes from these earliest progenitors. Importantly, the multipotent hematopoietic cells, which lack the differentiation potential into primitive erythroid cells, down-regulated these genes during a transition from the earliest committed progenitors. In addition, we showed that Pu.1 is involved in the multipotent cell differentiation through the suppression of erythroid transcription program. We propose that these molecular mechanisms governed by transcription factors form sequential waves of primitive erythropoiesis and multi-lineage hematopoiesis in the early yolk sac of developing embryos. J. Cell. Physiol. 232: 323-330, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Japan. yamanet@doc.medic.mie-u.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Washino
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Isono
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D047108:Embryonic Development; D004912:Erythrocytes / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006410:Hematopoiesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015017:Yolk Sac / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D017493:Leukocyte Common Antigens; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1