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Medial HOXA genes demarcate haematopoietic stem cell fate during human development
Pluripotent stem cells (PSC) may provide a potential source of haematopoietic stem/progenitor cells (HSPCs) for transplantation; however, unknown molecular barriers prevent the self-renewal of PSC-HSPCs. Using two-step differentiation, human embryonic stem cells (hESCs) differentiated in vitro into...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981340/ https://www.ncbi.nlm.nih.gov/pubmed/27183470 http://dx.doi.org/10.1038/ncb3354 |
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author | Dou, Diana R. Calvanese, Vincenzo Sierra, Maria I. Nguyen, Andrew T. Minasian, Arazin Saarikoski, Pamela Sasidharan, Rajkumar Ramirez, Christina M. Zack, Jerome A. Crooks, Gay M. Galic, Zoran Mikkola, Hanna K.A. |
author_facet | Dou, Diana R. Calvanese, Vincenzo Sierra, Maria I. Nguyen, Andrew T. Minasian, Arazin Saarikoski, Pamela Sasidharan, Rajkumar Ramirez, Christina M. Zack, Jerome A. Crooks, Gay M. Galic, Zoran Mikkola, Hanna K.A. |
author_sort | Dou, Diana R. |
collection | PubMed |
description | Pluripotent stem cells (PSC) may provide a potential source of haematopoietic stem/progenitor cells (HSPCs) for transplantation; however, unknown molecular barriers prevent the self-renewal of PSC-HSPCs. Using two-step differentiation, human embryonic stem cells (hESCs) differentiated in vitro into multipotent haematopoietic cells that had CD34(+)CD38(−/lo)CD90(+)CD45(+)GPI-80(+) foetal liver (FL) HSC immunophenotype, but displayed poor expansion potential and engraftment ability. Transcriptome analysis of immunophenotypic hESC-HSPCs revealed that, despite their molecular resemblance to FL-HSPCs, medial HOXA genes remained suppressed. Knockdown of HOXA7 disrupted FL-HSPC function and caused transcriptome dysregulation that resembled hESC-derived progenitors. Overexpression of medial HOXA genes prolonged FL-HSPC maintenance but was insufficient to confer self-renewal to hESC-HSPCs. Stimulation of retinoic acid signalling during endothelial-to-haematopoietic transition induced the HOXA cluster and other HSC/definitive haemogenic endothelium genes, and prolonged HSPC maintenance in culture. Thus, retinoic acid signalling-induced medial HOXA gene expression marks the establishment of the definitive HSC fate and controls HSC identity and function. |
format | Online Article Text |
id | pubmed-4981340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-49813402016-11-16 Medial HOXA genes demarcate haematopoietic stem cell fate during human development Dou, Diana R. Calvanese, Vincenzo Sierra, Maria I. Nguyen, Andrew T. Minasian, Arazin Saarikoski, Pamela Sasidharan, Rajkumar Ramirez, Christina M. Zack, Jerome A. Crooks, Gay M. Galic, Zoran Mikkola, Hanna K.A. Nat Cell Biol Article Pluripotent stem cells (PSC) may provide a potential source of haematopoietic stem/progenitor cells (HSPCs) for transplantation; however, unknown molecular barriers prevent the self-renewal of PSC-HSPCs. Using two-step differentiation, human embryonic stem cells (hESCs) differentiated in vitro into multipotent haematopoietic cells that had CD34(+)CD38(−/lo)CD90(+)CD45(+)GPI-80(+) foetal liver (FL) HSC immunophenotype, but displayed poor expansion potential and engraftment ability. Transcriptome analysis of immunophenotypic hESC-HSPCs revealed that, despite their molecular resemblance to FL-HSPCs, medial HOXA genes remained suppressed. Knockdown of HOXA7 disrupted FL-HSPC function and caused transcriptome dysregulation that resembled hESC-derived progenitors. Overexpression of medial HOXA genes prolonged FL-HSPC maintenance but was insufficient to confer self-renewal to hESC-HSPCs. Stimulation of retinoic acid signalling during endothelial-to-haematopoietic transition induced the HOXA cluster and other HSC/definitive haemogenic endothelium genes, and prolonged HSPC maintenance in culture. Thus, retinoic acid signalling-induced medial HOXA gene expression marks the establishment of the definitive HSC fate and controls HSC identity and function. 2016-05-16 2016-06 /pmc/articles/PMC4981340/ /pubmed/27183470 http://dx.doi.org/10.1038/ncb3354 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Dou, Diana R. Calvanese, Vincenzo Sierra, Maria I. Nguyen, Andrew T. Minasian, Arazin Saarikoski, Pamela Sasidharan, Rajkumar Ramirez, Christina M. Zack, Jerome A. Crooks, Gay M. Galic, Zoran Mikkola, Hanna K.A. Medial HOXA genes demarcate haematopoietic stem cell fate during human development |
title | Medial HOXA genes demarcate haematopoietic stem cell fate during human development |
title_full | Medial HOXA genes demarcate haematopoietic stem cell fate during human development |
title_fullStr | Medial HOXA genes demarcate haematopoietic stem cell fate during human development |
title_full_unstemmed | Medial HOXA genes demarcate haematopoietic stem cell fate during human development |
title_short | Medial HOXA genes demarcate haematopoietic stem cell fate during human development |
title_sort | medial hoxa genes demarcate haematopoietic stem cell fate during human development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981340/ https://www.ncbi.nlm.nih.gov/pubmed/27183470 http://dx.doi.org/10.1038/ncb3354 |
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