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Glycosylation Orchestrates Megakaryocytic Fate of Hematopoietic Stem Cells via Wnt-Muc13 Signaling [scRNA]

ABSTRACT: The cell-intrinsic and extrinsic programs governing hematopoietic stem and progenitor cells (HSPCs) cell fate determination remain unresolved. Our data reveals that loss of B4GALT1 glycosyltransferase biosynthetic activity restricts HSPC N- and O-glycosylation and reprograms previously unrecognized N-glycan gradients in the bone marrow environment with high expression of complex N-glycans in HSPC-rich regions to accumulate aberrant, cancer-like N-glycan signatures. The loss of B4GALT1 increases the expression of aberrantly glycosylated intracellular oncogenic Mucin13, which is likely to disrupt the destruction complex and mediate Wnt/β-catenin hyperactivation. This enhances metabolic and cell cycle activity, expands the megakaryocyte-primed stem cell pool, and promotes emergence from a steady state, highlighting the essential role of B4GALT1 in modulating the BM glycosylation landscape and its significance in regulating the expansion and differentiation of HSPCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE264078 | GEO | 2026/06/03

REPOSITORIES: GEO

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Glycosylation Orchestrates Megakaryocytic Fate of Hematopoietic Stem Cells via Wnt-Muc13 Signaling [bulkRNA]

Project description:The cell-intrinsic and extrinsic programs governing hematopoietic stem and progenitor cells (HSPCs) cell fate determination remain unresolved. Our data reveals that loss of B4GALT1 glycosyltransferase biosynthetic activity restricts HSPC N- and O-glycosylation and reprograms previously unrecognized N-glycan gradients in the bone marrow environment with high expression of complex N-glycans in HSPC-rich regions to accumulate aberrant, cancer-like N-glycan signatures. The loss of B4GALT1 increases the expression of aberrantly glycosylated intracellular oncogenic Mucin13, which is likely to disrupt the destruction complex and mediate Wnt/β-catenin hyperactivation. This enhances metabolic and cell cycle activity, expands the megakaryocyte-primed stem cell pool, and promotes emergence from a steady state, highlighting the essential role of B4GALT1 in modulating the BM glycosylation landscape and its significance in regulating the expansion and differentiation of HSPCs.

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Glycosylation Orchestrates Megakaryocytic Fate of Hematopoietic Stem Cells via Wnt-Muc13 Signaling [scMultiome]

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Project description:This SuperSeries is composed of the SubSeries listed below.