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| Status |
Public on Dec 15, 2020 |
| Title |
Recapitulation of murine thymopoiesis in vitro from single hematopoietic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We report a serum-free, 3-D murine artificial thymic organoid (ATO) system that mimics normal murine thymopoiesis from four different mouse strains with the production of all T cell populations, from early thymic progenitors to functional single positive (CD8SP and CD4SP) TCRabï€ and TCRyd cells. RNA sequencing aligned ATO-derived populations with phenotypically identical primary thymocytes. ATOs initiated with Rag1-/- marrow produced the same differentiation block as seen in the endogenous thymus, and Notch signaling patterns in ATOs mirrored primary thymopoiesis. ATOs initiated with defined hematopoietic stem cells (HSCs) and progenitors from marrow and thymus recapitulated subsequent stages and the normal kinetics of T cell differentiation. Remarkably, a single HSC deposited into ATOs generated a complete trajectory of T cell differentiation producing a similar diverse TCR repertoire across clones. ATOs represent a technically simple, highly reproducible and powerful experimental platform for the study of clonal thymopoiesis from HSCs.
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| Overall design |
Our goal was to analyze and compare the transcriptome of murine thymocyte populations generated in Artificial Thymic Organoids (ATOs) from murine bone marrow-derived hematopoietic stem cells with that of murine thymocyte populations isolated from primary thymus.
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| Contributor(s) |
Montel-Hagen A, Sun V, Casero D, Tsai S, Zampieri A, Jackson N, Li S, Lopez S, Zhu Y, Chick B, Chin CJ, Seet CS, Crooks GM |
| Citation(s) |
33113379 |
| Submission date |
Mar 02, 2020 |
| Last update date |
Dec 15, 2020 |
| Contact name |
Gay Miriam Crooks |
| E-mail(s) |
gcrooks@mednet.ucla.edu
|
| Phone |
3102060205
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| Organization name |
University of California Los Angeles
|
| Department |
Pathology & Laboratory Med
|
| Street address |
610 Charles E. Young Drive, East
|
| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA609734 |
| SRA |
SRP251280 |
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