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Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage\u2010specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of\n                    <jats:italic>Hira<\/jats:italic>\n                    in tyrosinase+ neural crest\u2010derived lineages, including melanoblasts, led to reduced melanoblast numbers during embryogenesis, with single\u2010cell RNA sequencing analysis indicating evidence of lineage\u2010specificity defects. This was supported in an in\u00a0vitro model using melb\u2010a melanoblasts in which\n                    <jats:italic>Hira<\/jats:italic>\n                    knockdown affected lineage identity and melanoblast differentiation potential, with ATAC\u2010seq data indicating a role of HIRA in orchestrating chromatin accessibility. Interestingly, however, newborn\n                    <jats:italic>Hira<\/jats:italic>\n                    knockout mice had wild type numbers of differentiated melanocytes, albeit functionally defective, as demonstrated by very mild hypopigmentation of the first hair coat, increased melanocyte telomere\u2010associated DNA damage foci, and impaired response to proliferative challenge. Moreover, as they aged, mice with embryonic melanoblast\n                    <jats:italic>Hira<\/jats:italic>\n                    knockout displayed marked defects in melanocyte stem cell maintenance and premature hair graying. Importantly, this phenotype was not observed after postnatal inducible knockout, indicating an essential role for HIRA at embryonic stages that is transmitted to adulthood, rather than a direct postnatal requirement within the pigmentary system. This genetic model shows that HIRA function during early development lays a foundation for maintaining lineage identity and subsequent maintenance of adult tissue\u2010specific stem cells during aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70070","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T01:42:42Z","timestamp":1747273362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inactivation of Histone Chaperone\n                    <scp>HIRA<\/scp>\n                    Unmasks a Link Between Normal Embryonic Development of Melanoblasts and Maintenance of Adult Melanocyte Stem Cells"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6094-751X","authenticated-orcid":false,"given":"Farah","family":"Jaber\u2010Hijazi","sequence":"first","affiliation":[{"name":"School of Cancer Sciences University of Glasgow  Glasgow 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