GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305059/primaryOK200TranscriptomicsDanio rerioExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305059GEOGSEfalseMutation of Tubgcp6 induces hematopoietic stem and progenitor cell exhaustion in zebrafishHematopoietic stem and progenitor cells (HSPCs) sustain blood cell production by balancing self-renewal and differentiation. While regulatory networks of transcription factors are well established during development of these cells, intrinsic cytoskeletal elements remain unclear. Here we show that the gamma-tubulin ring complex (γ-TuRC), a key regulator of microtubule nucleation, is essential for HSPC expansion in zebrafish. Forward genetic screening identifies the zebrafish smu1347 mutant, which exhibits HSPC exhaustion during definitive hematopoiesis. Positional cloning reveals a nonsense mutation in the tubgcp6 gene, encoding a core component of γ-TuRC, as responsible for the smu1347 phenotype. Mutation of Tubgcp6 causes mitotic arrest, disorganized spindle formation, and increased p53-dependent apoptosis. Time-lapse imaging and lineage tracing further demonstrate that Tubgcp6-deficient HSPCs preferentially undergo symmetric differentiation rather than self-renewal. Disrupting other γ-TuRC subunits (Tubgcp3, Tubgcp4, Tubgcp5) produces similar hematopoietic defects, underscoring the importance of intact microtubule nucleation for stem cell maintenance. These findings identify γ-TuRC-mediated microtubule organization as a critical regulator of HSPC fate and suggest that Tubgcp6 may represent a potential therapeutic target for bone marrow failure syndromes and stem cell exhaustion disorders.2026/04/15GSE305059GSM9161544GSM9161546GSM9161545GSM916154724995305059Danio rerio