biostudies-literatureKalaitzidis DNIA NIH HHSNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNCI NIH HHSNIH HHS1405-1413https://www.ebi.ac.uk/biostudies/studies/S-EPMC5373863biostudies-literatureUnknown127(4)The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve. In nutrient-abundant conditions, RagA-deficient HSC were functionally unimpaired and upregulated mTORThe Journal of clinical investigationAmino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells.PMC5373863R01 AI047389U01 HL100402R01 HL044851K01 DK092300R01 CA129105P01 HL131477R21 AG042876R01 HL097794R01 CA103866R37 AI047389DP5 OD012146Victora GDMercier FEKfoury YSykes DBLee DBaryawno NSabatini DMNeuberg DScadden DTPapazian ANayyar NKalaitzidis DEfeyan AfalseAmino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells.The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve. In nutrient-abundant conditions, RagA-deficient HSC were functionally unimpaired and upregulated mTOR2017-01-01T00:00:00Z2017 Apr2026-05-05T17:15:34.597Z2026-04-07T21:53:42.966ZS-EPMC53738632831904810.1172/JCI8945210.1172/jci89452