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Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs...

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Autores principales: Tang, Wanbo, He, Jian, Huang, Tao, Bai, Zhijie, Wang, Chaojie, Wang, Haizhen, Yang, Ruichuang, Ni, Yanli, Hou, Jun, Wang, Junliang, Zhou, Jie, Yao, Yingpeng, Gong, Yandong, Hou, Siyuan, Liu, Bing, Lan, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473784/
https://www.ncbi.nlm.nih.gov/pubmed/34589491
http://dx.doi.org/10.3389/fcell.2021.728057
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author Tang, Wanbo
He, Jian
Huang, Tao
Bai, Zhijie
Wang, Chaojie
Wang, Haizhen
Yang, Ruichuang
Ni, Yanli
Hou, Jun
Wang, Junliang
Zhou, Jie
Yao, Yingpeng
Gong, Yandong
Hou, Siyuan
Liu, Bing
Lan, Yu
author_facet Tang, Wanbo
He, Jian
Huang, Tao
Bai, Zhijie
Wang, Chaojie
Wang, Haizhen
Yang, Ruichuang
Ni, Yanli
Hou, Jun
Wang, Junliang
Zhou, Jie
Yao, Yingpeng
Gong, Yandong
Hou, Siyuan
Liu, Bing
Lan, Yu
author_sort Tang, Wanbo
collection PubMed
description In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45(–) and CD45(+) pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45(–) counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45(+) E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.
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spelling pubmed-84737842021-09-28 Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate Tang, Wanbo He, Jian Huang, Tao Bai, Zhijie Wang, Chaojie Wang, Haizhen Yang, Ruichuang Ni, Yanli Hou, Jun Wang, Junliang Zhou, Jie Yao, Yingpeng Gong, Yandong Hou, Siyuan Liu, Bing Lan, Yu Front Cell Dev Biol Cell and Developmental Biology In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45(–) and CD45(+) pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45(–) counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45(+) E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development. Frontiers Media S.A. 2021-09-13 /pmc/articles/PMC8473784/ /pubmed/34589491 http://dx.doi.org/10.3389/fcell.2021.728057 Text en Copyright © 2021 Tang, He, Huang, Bai, Wang, Wang, Yang, Ni, Hou, Wang, Zhou, Yao, Gong, Hou, Liu and Lan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Tang, Wanbo
He, Jian
Huang, Tao
Bai, Zhijie
Wang, Chaojie
Wang, Haizhen
Yang, Ruichuang
Ni, Yanli
Hou, Jun
Wang, Junliang
Zhou, Jie
Yao, Yingpeng
Gong, Yandong
Hou, Siyuan
Liu, Bing
Lan, Yu
Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
title Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
title_full Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
title_fullStr Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
title_full_unstemmed Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
title_short Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
title_sort hlf expression marks early emergence of hematopoietic stem cell precursors with adult repopulating potential and fate
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473784/
https://www.ncbi.nlm.nih.gov/pubmed/34589491
http://dx.doi.org/10.3389/fcell.2021.728057
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