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They are characterized by anemia, other hematopoietic and developmental abnormalities, and p53 activation. Ribosome assembly requires coordinated expression of many ribosomal protein (\n                    <jats:italic>RP<\/jats:italic>\n                    ) genes; however, the regulation of\n                    <jats:italic>RP<\/jats:italic>\n                    gene expression, especially in hematopoietic stem cells (HSCs), remains poorly understood. MYSM1 is a transcriptional regulator essential for HSC function and hematopoiesis. We established that HSC dysfunction in\n                    <jats:italic>Mysm1<\/jats:italic>\n                    deficiency is driven by p53; however, the mechanisms of p53 activation remained unclear. Here, we describe the transcriptome of\n                    <jats:italic>Mysm1<\/jats:italic>\n                    -deficient mouse HSCs and identify MYSM1 genome-wide DNA binding sites. We establish a direct role for MYSM1 in\n                    <jats:italic>RP<\/jats:italic>\n                    gene expression and show a reduction in protein synthesis in\n                    <jats:italic>Mysm1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    HSCs. Loss of p53 in mice fully rescues\n                    <jats:italic>Mysm1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    anemia phenotype but not\n                    <jats:italic>RP<\/jats:italic>\n                    gene expression, indicating that\n                    <jats:italic>RP<\/jats:italic>\n                    gene dysregulation is a direct outcome of\n                    <jats:italic>Mysm1<\/jats:italic>\n                    deficiency and an upstream mediator of\n                    <jats:italic>Mysm1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    phenotypes through p53 activation. We characterize a patient with a homozygous nonsense\n                    <jats:italic>MYSM1<\/jats:italic>\n                    gene variant, and we demonstrate reduced protein synthesis and increased p53 levels in patient hematopoietic cells. Our work provides insights into the specialized mechanisms regulating\n                    <jats:italic>RP<\/jats:italic>\n                    gene expression in HSCs and establishes a common etiology of\n                    <jats:italic>MYSM1<\/jats:italic>\n                    deficiency and ribosomopathy syndromes.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.125690","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T11:01:18Z","timestamp":1594206078000},"source":"Crossref","is-referenced-by-count":27,"title":["MYSM1 maintains ribosomal protein gene expression in hematopoietic stem cells to prevent hematopoietic dysfunction"],"prefix":"10.1172","volume":"5","author":[{"given":"Jad I.","family":"Belle","sequence":"first","affiliation":[{"name":"Department of Physiology,"},{"name":"McGill University Research Centre on Complex Traits, 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