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Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors.

J Exp Med. 2019 Jul 01;216(7):1599-1614. Epub 2019 May 10
Tomomasa Yokomizo 1 , Naoki Watanabe 2 , Terumasa Umemoto 3 , Junichi Matsuo 1 , Ryota Harai 3 , Yoshihiko Kihara 4 , Eri Nakamura 5 , Norihiro Tada 5 , Tomohiko Sato 6 , Tomoiku Takaku 2 , Akihiko Shimono 1 , Hitoshi Takizawa 3 , Naomi Nakagata 7 , Seiichi Mori 8 , Mineo Kurokawa 6 , Daniel G Tenen 9 , Motomi Osato 1 , Toshio Suda 1 , Norio Komatsu 2
Tomomasa Yokomizo 1 , Naoki Watanabe 2 , Terumasa Umemoto 3 , Junichi Matsuo 1 , Ryota Harai 3 , Yoshihiko Kihara 4 , Eri Nakamura 5 , Norihiro Tada 5 , Tomohiko Sato 6 , Tomoiku Takaku 2 , Akihiko Shimono 1 , Hitoshi Takizawa 3 , Naomi Nakagata 7 , Seiichi Mori 8 , Mineo Kurokawa 6 , Daniel G Tenen 9 , Motomi Osato 1 , Toshio Suda 1 , Norio Komatsu 2
+ et al

[No authors listed]

Author information
  • 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore.
  • 2 Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 3 International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • 4 Leading Center for the Development and Research of Cancer Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 5 Laboratory of Genome Research, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 6 Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 7 Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
  • 8 Division of Cancer Genomics, Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 9 Harvard Stem Cell Institute, Boston, MA.

摘要

Before the emergence of hematopoietic stem cells (HSCs), lineage-restricted progenitors, such as erythro-myeloid progenitors (EMPs), are detected in the embryo or in pluripotent stem cell cultures in vitro. Although both HSCs and EMPs are derived from hemogenic endothelium, it remains unclear how and when these two developmental programs are segregated during ontogeny. Here, we show that hepatic leukemia factor (Hlf) expression specifically marks a developmental continuum between HSC precursors and HSCs. Using the Hlf-tdTomato reporter mouse, we found that Hlf is expressed in intra-aortic hematopoietic clusters and fetal liver HSCs. In contrast, EMPs and yolk sac hematopoietic clusters before embryonic day 9.5 do not express Hlf HSC specification, regulated by the Evi-1/Hlf axis, is activated only within Hlf+ nascent hematopoietic clusters. These results strongly suggest that HSCs and EMPs are generated from distinct cohorts of hemogenic endothelium. Selective induction of the Hlf+ lineage pathway may lead to the in vitro generation of HSCs from pluripotent stem cells.

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