Strength of CAR signaling determines T cell versus ILC differentiation from pluripotent stem cells.

Generation of chimeric antigen receptor (CAR) T cells from pluripotent stem cells (PSCs) will enable advances in cancer immunotherapy. Understanding how CARs affect T cell differentiation from PSCs is important for this effort. The recently described artificial thymic organoid (ATO) system supports in vitro differentiation of PSCs to T cells.

The Metabolic Landscape of Thymic T Cell Development and .

Although metabolic pathways have been shown to control differentiation and activation in peripheral T cells, metabolic studies on thymic T cell development are still lacking, especially in human tissue. In this study, we use transcriptomics and extracellular flux analyses to investigate the metabolic profiles of primary thymic and -derived mouse and human thymocytes. Core metabolic pathways, specifically glycolysis and oxidative phosphorylation, undergo dramatic changes between the double-negative (DN), double-positive (DP), and mature single-positive (SP) stages in murine and human thymus.

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 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.

Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells.

The ability to generate T cells from pluripotent stem cells (PSCs) has the potential to transform autologous T cell immunotherapy by facilitating universal, off-the-shelf cell products. However, differentiation of human PSCs into mature, conventional T cells has been challenging with existing methods. We report that a continuous 3D organoid system induced an orderly sequence of commitment and differentiation from PSC-derived embryonic mesoderm through hematopoietic specification and efficient terminal differentiation to naive CD3CD8αβ and CD3CD4 conventional T cells with a diverse T cell receptor (TCR) repertoire.

Impact of motor task execution on an individual's ability to mirror forearm positions.

This work is motivated by our goal of determining why individuals with stroke are impaired when locating their arms in space. We assessed the ability of individuals without neurological impairments to mirror their forearms during various motor tasks so that we could identify baseline performance in an unimpaired population. Nine right-hand dominant participants without neurological impairments mirrored forearm positions bi-directionally (i.

Lumen Formation Is an Intrinsic Property of Isolated Human Pluripotent Stem Cells.

We demonstrate that dissociated human pluripotent stem cells (PSCs) are intrinsically programmed to form lumens. PSCs form two-cell cysts with a shared apical domain within 20 hr of plating; these cysts collapse to form monolayers after 5 days. Expression of pluripotency markers is maintained throughout this time.