| First Author | Montel-Hagen A | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 4 | Pages | 108320 |
| PubMed ID | 33113379 | Mgi Jnum | J:315004 |
| Mgi Id | MGI:6714741 | Doi | 10.1016/j.celrep.2020.108320 |
| Citation | Montel-Hagen A, et al. (2020) In Vitro Recapitulation of Murine Thymopoiesis from Single Hematopoietic Stem Cells. Cell Rep 33(4):108320 |
| abstractText | 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) TCRalphabeta and TCRgammadelta 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. |
