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Here, we show that the transcription factor Helios is highly expressed in murine hematopoietic stem and progenitor cells (HSPCs), where it is required to suppress the separation of the platelet/megakaryocyte lineage from the HSPC pool. Helios acts mainly in quiescent cells, where it directly represses the megakaryocyte gene expression program in cells as early as the stem cell stage. Helios binding promotes chromatin compaction, notably at the regulatory regions of platelet-specific genes recognized by the Gata2 and Runx1 transcriptional activators, implicated in megakaryocyte priming. Helios null HSPCs are biased toward the megakaryocyte lineage at the expense of the lymphoid and partially resemble cells of aging animals. We propose that Helios acts as a guardian of HSPC pluripotency by continuously repressing the megakaryocyte fate, which in turn allows downstream lymphoid priming to take place. These results highlight the importance of negative and positive priming events in lineage commitment. Overall design: Longitudinally sampled PBMC and CAR T sorted samples"],"repository":["ENA"],"description_synonyms":["CMAR, Thymus-Dependent Lymphocytes, CVB3-binding protein, 2610206D03Rik, Constitutive androstane receptor, SPG5C, CAR-beta, Orphan nuclear receptor MB67, CaR, NSHPT, T-Lymphocyte, Constitutive active response, LEU5, GPRC2A, DLEU5, Cell, Cars, ADOHR, Automobile, Constitutive activator of retinoid response, T Lymphocyte, AW553441, T-Cell, actomyosin ring, RFP2, Rfp2, ESTM32, MCVADR, CAR4|6, CAR, MB67, Car, PGN, CNC, HCVADR, HHC, RNF77, AU016810, 3110001L12Rik, FHH, PCAR1, AA209988, HCAR, T-Cells, Coxsackievirus B-adenovirus receptor, Thymus-Dependent, T, EIG8, Lymphocytes, PRKAR1, Thymus-Dependent Lymphocyte, Cytokine., CAR1, MCAR, T Cells, FIH, CNC1, contractile actomyosin ring, CAR4/6, TSE1, Gprc2a, ACRDYS1, Cells, HHC1, PPNAD1, cytokinetic ring, T Cell, constriction ring, HYPOC1, AI551208, T Lymphocytes, Thymus Dependent Lymphocytes, hCAR, Care2, Lymphocyte, PKR1"],"name_synonyms":["CMAR, Thymus-Dependent Lymphocytes, CVB3-binding protein, 2610206D03Rik, Constitutive androstane receptor, SPG5C, CAR-beta, Orphan nuclear receptor MB67, CaR, NSHPT, T-Lymphocyte, Constitutive active response, LEU5, GPRC2A, DLEU5, Cell, Cars, ADOHR, Automobile, Constitutive activator of retinoid response, T Lymphocyte, AW553441, T-Cell, actomyosin ring, RFP2, Rfp2, ESTM32, MCVADR, CAR4|6, CAR, MB67, Car, PGN, CNC, HCVADR, HHC, RNF77, AU016810, 3110001L12Rik, FHH, PCAR1, AA209988, HCAR, T-Cells, Coxsackievirus B-adenovirus receptor, Thymus-Dependent, T, EIG8, Lymphocytes, PRKAR1, Thymus-Dependent Lymphocyte, Cytokine., CAR1, MCAR, T Cells, FIH, CNC1, contractile actomyosin ring, CAR4/6, TSE1, Gprc2a, ACRDYS1, Cells, HHC1, PPNAD1, cytokinetic ring, T Cell, constriction ring, HYPOC1, AI551208, T Lymphocytes, Thymus Dependent Lymphocytes, hCAR, Care2, Lymphocyte, PKR1"],"additional_accession":[]},"is_claimable":false,"name":"CAR+ and CAR- T cells differentiate into an NK-like subset that is associated with increased inflammatory cytokines following infusion","description":"CAR+ and CAR- T cells differentiate into an NK-like subset that is associated with increased inflammatory cytokines following infusion","dates":{"last_updated":"2025-09-24","first_public":"2023-09-28"},"accession":"PRJNA931739","cross_references":{"GEO":["GSE224550"],"taxon":["9606"],"PubMed":["38012187"]}}