Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells
The functions of retinoic acid (RA), a potent morphogen with crucial roles in embryogenesis including developmental hematopoiesis, have not been thoroughly investigated in the human setting. Using an in vitro model of human hematopoietic development, we evaluated the effects of RA signaling on the d...
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doaj-f52466d4d56f4eaa8b415983b2090c502020-11-24T22:27:32ZengElsevierStem Cell Reports2213-67112015-02-014226928110.1016/j.stemcr.2015.01.009Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem CellsRoger E. Rönn0Carolina Guibentif1Roksana Moraghebi2Patricia Chaves3Shobhit Saxena4Bradley Garcia5Niels-Bjarne Woods6Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenStem Cell Laboratory, Lund University Stem Cell Center, Lund University, BMC B10, 221 84 Lund, SwedenDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenPrimorigen Biosciences, 510 Charmany Drive, Madison, WI 53719, USADepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenThe functions of retinoic acid (RA), a potent morphogen with crucial roles in embryogenesis including developmental hematopoiesis, have not been thoroughly investigated in the human setting. Using an in vitro model of human hematopoietic development, we evaluated the effects of RA signaling on the development of blood and on generated hematopoietic progenitors. Decreased RA signaling increases the generation of cells with a hematopoietic stem cell (HSC)-like phenotype, capable of differentiation into myeloid and lymphoid lineages, through two separate mechanisms: by increasing the commitment of pluripotent stem cells toward the hematopoietic lineage during the developmental process and by decreasing the differentiation of generated blood progenitors. Our results demonstrate that controlled low-level RA signaling is a requirement in human blood development, and we propose a new interpretation of RA as a regulatory factor, where appropriate control of RA signaling enables increased generation of hematopoietic progenitor cells from pluripotent stem cells in vitro.http://www.sciencedirect.com/science/article/pii/S2213671115000302 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roger E. Rönn Carolina Guibentif Roksana Moraghebi Patricia Chaves Shobhit Saxena Bradley Garcia Niels-Bjarne Woods |
spellingShingle |
Roger E. Rönn Carolina Guibentif Roksana Moraghebi Patricia Chaves Shobhit Saxena Bradley Garcia Niels-Bjarne Woods Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells Stem Cell Reports |
author_facet |
Roger E. Rönn Carolina Guibentif Roksana Moraghebi Patricia Chaves Shobhit Saxena Bradley Garcia Niels-Bjarne Woods |
author_sort |
Roger E. Rönn |
title |
Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells |
title_short |
Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells |
title_full |
Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells |
title_fullStr |
Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells |
title_full_unstemmed |
Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells |
title_sort |
retinoic acid regulates hematopoietic development from human pluripotent stem cells |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2015-02-01 |
description |
The functions of retinoic acid (RA), a potent morphogen with crucial roles in embryogenesis including developmental hematopoiesis, have not been thoroughly investigated in the human setting. Using an in vitro model of human hematopoietic development, we evaluated the effects of RA signaling on the development of blood and on generated hematopoietic progenitors. Decreased RA signaling increases the generation of cells with a hematopoietic stem cell (HSC)-like phenotype, capable of differentiation into myeloid and lymphoid lineages, through two separate mechanisms: by increasing the commitment of pluripotent stem cells toward the hematopoietic lineage during the developmental process and by decreasing the differentiation of generated blood progenitors. Our results demonstrate that controlled low-level RA signaling is a requirement in human blood development, and we propose a new interpretation of RA as a regulatory factor, where appropriate control of RA signaling enables increased generation of hematopoietic progenitor cells from pluripotent stem cells in vitro. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671115000302 |
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