Transcriptional Activation of Regenerative Hematopoiesis via Vascular Niche Sensing.

TitleTranscriptional Activation of Regenerative Hematopoiesis via Vascular Niche Sensing.
Publication TypeJournal Article
Year of Publication2023
AuthorsItkin T, Houghton S, Schreiner R, Lin Y, Badwe CR, Voisin V, Murison A, Seyedhassantehrani N, Kaufmann KB, Garcia-Prat L, Booth GT, Geng F, Liu Y, Gomez-Salinero JM, Shieh J-H, Redmond D, Xiang JZ, Josefowicz SZ, Trapnell C, Spencer JA, Zangi L, Hadland B, Dick JE, Xie SZ, Rafii S
Date Published2023 Mar 29

Transition between activation and quiescence programs in hematopoietic stem and progenitor cells (HSC/HSPCs) is perceived to be governed intrinsically and by microenvironmental co-adaptation. However, HSC programs dictating both transition and adaptability, remain poorly defined. Single cell multiome analysis divulging differential transcriptional activity between distinct HSPC states, indicated for the exclusive absence of Fli-1 motif from quiescent HSCs. We reveal that Fli-1 activity is essential for HSCs during regenerative hematopoiesis. Fli-1 directs activation programs while manipulating cellular sensory and output machineries, enabling HSPCs co-adoptability with a stimulated vascular niche. During regenerative conditions, Fli-1 presets and enables propagation of niche-derived Notch1 signaling. Constitutively induced Notch1 signaling is sufficient to recuperate functional HSC impairments in the absence of Fli-1. Applying FLI-1 modified-mRNA transduction into lethargic adult human mobilized HSPCs, enables their vigorous niche-mediated expansion along with superior engraftment capacities. Thus, decryption of stem cell activation programs offers valuable insights for immune regenerative medicine.

Alternate JournalbioRxiv
PubMed ID37034724
PubMed Central IDPMC10081204
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