Hematopoietic stem cells undergo bidirectional fate transitions in vivo
Abstract
Differentiation of haematopoietic stem and progenitor cells (HSPCs) is widely considered unidirectional in vivo. Here, we developed clonal phylogenetic tracing (CP-tracer) by sequential genetic barcoding, which enabled high-resolution analysis of 181,695 subclones derived from 847 individually labelled HSPCs. This approach uncovered bidirectional fate transitions between myeloid-biased (My-) and lineage-balanced haematopoietic stem cells (HSCs). Individual HSC clones, distinguished by temporally unique serial barcodes, exhibited durable lineage bidirectionality, with dynamics favouring progressive accumulation of My-HSCs over time. CRISPR-Cas9 screening identified the homeobox gene Hhex as a suppressor of myeloid differentiation that enables pivoting toward balanced output. Hhex function is age-dependent, with its expression declining in aged HSCs. Together, these findings demonstrate unexpected plasticity in HSC differentiation, modulated in part by Hhex-mediated repression, that shifts over time to drive the myeloid bias characteristic of ageing.
Lifecycle
- biorxiv v3 2026-07-08 source ↗
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RRID Robot @rridrobot.bsky.social · 120 followers neutral
A paper using RRID:Addgene_85995 was just published in Rxiv see "Hematopoietic stem cells undergo bidirectional fate transitions in vivo". RRIDs like this improve reproducibility in scientific research. #RRID #OpenScience
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RRID Robot @rridrobot.bsky.social · 120 followers neutral
A preprint using: pMJ114 (RRID:Addgene_85995) from #Addgene was published. SciScore made a table with this resource, see “Automated Services” module (download as csv, xml or #jats) #methodsmatter #RRID