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In Vitro Recapitulation of Murine Thymopoiesis from Single Hematopoietic Stem Cells
We report a serum-free, 3D murine artificial thymic organoid (M-ATO) system that mimics normal murine thymopoiesis with the production of all T cell stages, from early thymic progenitors to functional single-positive (CD8SP and CD4SP) TCRαβ and TCRγδ cells. RNA sequencing aligns M-ATO-derived popula...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727762/ https://www.ncbi.nlm.nih.gov/pubmed/33113379 http://dx.doi.org/10.1016/j.celrep.2020.108320 |
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author | Montel-Hagen, Amélie Sun, Victoria Casero, David Tsai, Steven Zampieri, Alexandre Jackson, Nicholas Li, Suwen Lopez, Shawn Zhu, Yuhua Chick, Brent He, Chongbin de Barros, Stéphanie C. Seet, Christopher S. Crooks, Gay M. |
author_facet | Montel-Hagen, Amélie Sun, Victoria Casero, David Tsai, Steven Zampieri, Alexandre Jackson, Nicholas Li, Suwen Lopez, Shawn Zhu, Yuhua Chick, Brent He, Chongbin de Barros, Stéphanie C. Seet, Christopher S. Crooks, Gay M. |
author_sort | Montel-Hagen, Amélie |
collection | PubMed |
description | We report a serum-free, 3D murine artificial thymic organoid (M-ATO) system that mimics normal murine thymopoiesis with the production of all T cell stages, from early thymic progenitors to functional single-positive (CD8SP and CD4SP) TCRαβ and TCRγδ cells. RNA sequencing aligns M-ATO-derived populations with phenotypically identical primary thymocytes. M-ATOs initiated with Rag1(−/−) marrow produce the same differentiation block as seen in the endogenous thymus, and Notch signaling patterns in M-ATOs mirror primary thymopoiesis. M-ATOs initiated with defined hematopoietic stem cells (HSCs) and lymphoid progenitors from marrow and thymus generate each of the downstream differentiation stages, allowing the kinetics of T cell differentiation to be tracked. Remarkably, single HSCs deposited into each M-ATO generate the complete trajectory of T cell differentiation, producing diverse TCR repertoires across clones that largely match endogenous thymus. M-ATOs represent a highly reproducible and efficient experimental platform for the interrogation of clonal thymopoiesis from HSCs. |
format | Online Article Text |
id | pubmed-7727762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-77277622020-12-10 In Vitro Recapitulation of Murine Thymopoiesis from Single Hematopoietic Stem Cells Montel-Hagen, Amélie Sun, Victoria Casero, David Tsai, Steven Zampieri, Alexandre Jackson, Nicholas Li, Suwen Lopez, Shawn Zhu, Yuhua Chick, Brent He, Chongbin de Barros, Stéphanie C. Seet, Christopher S. Crooks, Gay M. Cell Rep Article We report a serum-free, 3D murine artificial thymic organoid (M-ATO) system that mimics normal murine thymopoiesis with the production of all T cell stages, from early thymic progenitors to functional single-positive (CD8SP and CD4SP) TCRαβ and TCRγδ cells. RNA sequencing aligns M-ATO-derived populations with phenotypically identical primary thymocytes. M-ATOs initiated with Rag1(−/−) marrow produce the same differentiation block as seen in the endogenous thymus, and Notch signaling patterns in M-ATOs mirror primary thymopoiesis. M-ATOs initiated with defined hematopoietic stem cells (HSCs) and lymphoid progenitors from marrow and thymus generate each of the downstream differentiation stages, allowing the kinetics of T cell differentiation to be tracked. Remarkably, single HSCs deposited into each M-ATO generate the complete trajectory of T cell differentiation, producing diverse TCR repertoires across clones that largely match endogenous thymus. M-ATOs represent a highly reproducible and efficient experimental platform for the interrogation of clonal thymopoiesis from HSCs. 2020-10-27 /pmc/articles/PMC7727762/ /pubmed/33113379 http://dx.doi.org/10.1016/j.celrep.2020.108320 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Montel-Hagen, Amélie Sun, Victoria Casero, David Tsai, Steven Zampieri, Alexandre Jackson, Nicholas Li, Suwen Lopez, Shawn Zhu, Yuhua Chick, Brent He, Chongbin de Barros, Stéphanie C. Seet, Christopher S. Crooks, Gay M. In Vitro Recapitulation of Murine Thymopoiesis from Single Hematopoietic Stem Cells |
title | In Vitro Recapitulation of Murine Thymopoiesis from
Single Hematopoietic Stem Cells |
title_full | In Vitro Recapitulation of Murine Thymopoiesis from
Single Hematopoietic Stem Cells |
title_fullStr | In Vitro Recapitulation of Murine Thymopoiesis from
Single Hematopoietic Stem Cells |
title_full_unstemmed | In Vitro Recapitulation of Murine Thymopoiesis from
Single Hematopoietic Stem Cells |
title_short | In Vitro Recapitulation of Murine Thymopoiesis from
Single Hematopoietic Stem Cells |
title_sort | in vitro recapitulation of murine thymopoiesis from
single hematopoietic stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727762/ https://www.ncbi.nlm.nih.gov/pubmed/33113379 http://dx.doi.org/10.1016/j.celrep.2020.108320 |
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