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Identification and characterization of in vitro expanded hematopoietic stem cells
Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200‐fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535767/ https://www.ncbi.nlm.nih.gov/pubmed/35971894 http://dx.doi.org/10.15252/embr.202255502 |
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author | Che, James L C Bode, Daniel Kucinski, Iwo Cull, Alyssa H Bain, Fiona Becker, Hans J Jassinskaja, Maria Barile, Melania Boyd, Grace Belmonte, Miriam Zeng, Andy G X Igarashi, Kyomi J Rubio‐Lara, Juan Shepherd, Mairi S Clay, Anna Dick, John E Wilkinson, Adam C Nakauchi, Hiromitsu Yamazaki, Satoshi Göttgens, Berthold Kent, David G |
author_facet | Che, James L C Bode, Daniel Kucinski, Iwo Cull, Alyssa H Bain, Fiona Becker, Hans J Jassinskaja, Maria Barile, Melania Boyd, Grace Belmonte, Miriam Zeng, Andy G X Igarashi, Kyomi J Rubio‐Lara, Juan Shepherd, Mairi S Clay, Anna Dick, John E Wilkinson, Adam C Nakauchi, Hiromitsu Yamazaki, Satoshi Göttgens, Berthold Kent, David G |
author_sort | Che, James L C |
collection | PubMed |
description | Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200‐fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non‐HSCs and single cell‐initiated cultures have substantial clone‐to‐clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non‐HSCs in expansion cultures. By directly linking single‐clone functional transplantation data with single‐clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This “repopulation signature” (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers. |
format | Online Article Text |
id | pubmed-9535767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95357672022-10-16 Identification and characterization of in vitro expanded hematopoietic stem cells Che, James L C Bode, Daniel Kucinski, Iwo Cull, Alyssa H Bain, Fiona Becker, Hans J Jassinskaja, Maria Barile, Melania Boyd, Grace Belmonte, Miriam Zeng, Andy G X Igarashi, Kyomi J Rubio‐Lara, Juan Shepherd, Mairi S Clay, Anna Dick, John E Wilkinson, Adam C Nakauchi, Hiromitsu Yamazaki, Satoshi Göttgens, Berthold Kent, David G EMBO Rep Articles Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200‐fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non‐HSCs and single cell‐initiated cultures have substantial clone‐to‐clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non‐HSCs in expansion cultures. By directly linking single‐clone functional transplantation data with single‐clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This “repopulation signature” (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers. John Wiley and Sons Inc. 2022-08-16 /pmc/articles/PMC9535767/ /pubmed/35971894 http://dx.doi.org/10.15252/embr.202255502 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Che, James L C Bode, Daniel Kucinski, Iwo Cull, Alyssa H Bain, Fiona Becker, Hans J Jassinskaja, Maria Barile, Melania Boyd, Grace Belmonte, Miriam Zeng, Andy G X Igarashi, Kyomi J Rubio‐Lara, Juan Shepherd, Mairi S Clay, Anna Dick, John E Wilkinson, Adam C Nakauchi, Hiromitsu Yamazaki, Satoshi Göttgens, Berthold Kent, David G Identification and characterization of in vitro expanded hematopoietic stem cells |
title | Identification and characterization of in vitro expanded hematopoietic stem cells |
title_full | Identification and characterization of in vitro expanded hematopoietic stem cells |
title_fullStr | Identification and characterization of in vitro expanded hematopoietic stem cells |
title_full_unstemmed | Identification and characterization of in vitro expanded hematopoietic stem cells |
title_short | Identification and characterization of in vitro expanded hematopoietic stem cells |
title_sort | identification and characterization of in vitro expanded hematopoietic stem cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535767/ https://www.ncbi.nlm.nih.gov/pubmed/35971894 http://dx.doi.org/10.15252/embr.202255502 |
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