| Title | Transcriptional Activation of Regenerative Hematopoiesis via Vascular Niche Sensing. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Itkin 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 |
| Journal | bioRxiv |
| Date Published | 2023 Mar 29 |
| ISSN | 2692-8205 |
| Abstract | <p>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.</p> |
| DOI | 10.1101/2023.03.27.534417 |
| Alternate Journal | bioRxiv |
| PubMed ID | 37034724 |
| PubMed Central ID | PMC10081204 |