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

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 an...

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Autores principales: Yokomizo, Tomomasa, Watanabe, Naoki, Umemoto, Terumasa, Matsuo, Junichi, Harai, Ryota, Kihara, Yoshihiko, Nakamura, Eri, Tada, Norihiro, Sato, Tomohiko, Takaku, Tomoiku, Shimono, Akihiko, Takizawa, Hitoshi, Nakagata, Naomi, Mori, Seiichi, Kurokawa, Mineo, Tenen, Daniel G., Osato, Motomi, Suda, Toshio, Komatsu, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605751/
https://www.ncbi.nlm.nih.gov/pubmed/31076455
http://dx.doi.org/10.1084/jem.20181399
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author Yokomizo, Tomomasa
Watanabe, Naoki
Umemoto, Terumasa
Matsuo, Junichi
Harai, Ryota
Kihara, Yoshihiko
Nakamura, Eri
Tada, Norihiro
Sato, Tomohiko
Takaku, Tomoiku
Shimono, Akihiko
Takizawa, Hitoshi
Nakagata, Naomi
Mori, Seiichi
Kurokawa, Mineo
Tenen, Daniel G.
Osato, Motomi
Suda, Toshio
Komatsu, Norio
author_facet Yokomizo, Tomomasa
Watanabe, Naoki
Umemoto, Terumasa
Matsuo, Junichi
Harai, Ryota
Kihara, Yoshihiko
Nakamura, Eri
Tada, Norihiro
Sato, Tomohiko
Takaku, Tomoiku
Shimono, Akihiko
Takizawa, Hitoshi
Nakagata, Naomi
Mori, Seiichi
Kurokawa, Mineo
Tenen, Daniel G.
Osato, Motomi
Suda, Toshio
Komatsu, Norio
author_sort Yokomizo, Tomomasa
collection PubMed
description 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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spelling pubmed-66057512020-01-01 Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors Yokomizo, Tomomasa Watanabe, Naoki Umemoto, Terumasa Matsuo, Junichi Harai, Ryota Kihara, Yoshihiko Nakamura, Eri Tada, Norihiro Sato, Tomohiko Takaku, Tomoiku Shimono, Akihiko Takizawa, Hitoshi Nakagata, Naomi Mori, Seiichi Kurokawa, Mineo Tenen, Daniel G. Osato, Motomi Suda, Toshio Komatsu, Norio J Exp Med Research Articles 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. Rockefeller University Press 2019-07-01 2019-05-10 /pmc/articles/PMC6605751/ /pubmed/31076455 http://dx.doi.org/10.1084/jem.20181399 Text en © 2019 Yokomizo et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Yokomizo, Tomomasa
Watanabe, Naoki
Umemoto, Terumasa
Matsuo, Junichi
Harai, Ryota
Kihara, Yoshihiko
Nakamura, Eri
Tada, Norihiro
Sato, Tomohiko
Takaku, Tomoiku
Shimono, Akihiko
Takizawa, Hitoshi
Nakagata, Naomi
Mori, Seiichi
Kurokawa, Mineo
Tenen, Daniel G.
Osato, Motomi
Suda, Toshio
Komatsu, Norio
Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
title Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
title_full Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
title_fullStr Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
title_full_unstemmed Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
title_short Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
title_sort hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605751/
https://www.ncbi.nlm.nih.gov/pubmed/31076455
http://dx.doi.org/10.1084/jem.20181399
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