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SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways

Hemogenic endothelium (HE) is the main source of blood cells in the embryo. To improve blood manufacturing from human pluripotent stem cells (hPSCs), it is essential to define the molecular determinants that enhance HE specification and promote development of the desired blood lineage from HE. Here,...

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Autores principales: Jung, Ho Sun, Suknuntha, Kran, Kim, Yun Hee, Liu, Peng, Dettle, Samuel T., Sedzro, Divine Mensah, Smith, Portia R., Thomson, James A., Ong, Irene M., Slukvin, Igor I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214392/
https://www.ncbi.nlm.nih.gov/pubmed/37250328
http://dx.doi.org/10.1016/j.isci.2023.106621
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author Jung, Ho Sun
Suknuntha, Kran
Kim, Yun Hee
Liu, Peng
Dettle, Samuel T.
Sedzro, Divine Mensah
Smith, Portia R.
Thomson, James A.
Ong, Irene M.
Slukvin, Igor I.
author_facet Jung, Ho Sun
Suknuntha, Kran
Kim, Yun Hee
Liu, Peng
Dettle, Samuel T.
Sedzro, Divine Mensah
Smith, Portia R.
Thomson, James A.
Ong, Irene M.
Slukvin, Igor I.
author_sort Jung, Ho Sun
collection PubMed
description Hemogenic endothelium (HE) is the main source of blood cells in the embryo. To improve blood manufacturing from human pluripotent stem cells (hPSCs), it is essential to define the molecular determinants that enhance HE specification and promote development of the desired blood lineage from HE. Here, using SOX18-inducible hPSCs, we revealed that SOX18 forced expression at the mesodermal stage, in contrast to its homolog SOX17, has minimal effects on arterial specification of HE, expression of HOXA genes and lymphoid differentiation. However, forced expression of SOX18 in HE during endothelial-to-hematopoietic transition (EHT) greatly increases NK versus T cell lineage commitment of hematopoietic progenitors (HPs) arising from HE predominantly expanding CD34(+)CD43(+)CD235a/CD41a(−)CD45(−) multipotent HPs and altering the expression of genes related to T cell and Toll-like receptor signaling. These studies improve our understanding of lymphoid cell specification during EHT and provide a new tool for enhancing NK cell production from hPSCs for immunotherapies.
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spelling pubmed-102143922023-05-27 SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways Jung, Ho Sun Suknuntha, Kran Kim, Yun Hee Liu, Peng Dettle, Samuel T. Sedzro, Divine Mensah Smith, Portia R. Thomson, James A. Ong, Irene M. Slukvin, Igor I. iScience Article Hemogenic endothelium (HE) is the main source of blood cells in the embryo. To improve blood manufacturing from human pluripotent stem cells (hPSCs), it is essential to define the molecular determinants that enhance HE specification and promote development of the desired blood lineage from HE. Here, using SOX18-inducible hPSCs, we revealed that SOX18 forced expression at the mesodermal stage, in contrast to its homolog SOX17, has minimal effects on arterial specification of HE, expression of HOXA genes and lymphoid differentiation. However, forced expression of SOX18 in HE during endothelial-to-hematopoietic transition (EHT) greatly increases NK versus T cell lineage commitment of hematopoietic progenitors (HPs) arising from HE predominantly expanding CD34(+)CD43(+)CD235a/CD41a(−)CD45(−) multipotent HPs and altering the expression of genes related to T cell and Toll-like receptor signaling. These studies improve our understanding of lymphoid cell specification during EHT and provide a new tool for enhancing NK cell production from hPSCs for immunotherapies. Elsevier 2023-04-08 /pmc/articles/PMC10214392/ /pubmed/37250328 http://dx.doi.org/10.1016/j.isci.2023.106621 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jung, Ho Sun
Suknuntha, Kran
Kim, Yun Hee
Liu, Peng
Dettle, Samuel T.
Sedzro, Divine Mensah
Smith, Portia R.
Thomson, James A.
Ong, Irene M.
Slukvin, Igor I.
SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
title SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
title_full SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
title_fullStr SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
title_full_unstemmed SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
title_short SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
title_sort sox18-enforced expression diverts hemogenic endothelium-derived progenitors from t towards nk lymphoid pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214392/
https://www.ncbi.nlm.nih.gov/pubmed/37250328
http://dx.doi.org/10.1016/j.isci.2023.106621
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