Abstract
AbstractDirect reprogramming of human fibroblasts into hematopoietic stem cells (HSCs) presents a promising strategy for overcoming the limitations of traditional bone-marrow transplantation. Despite the potential of this approach, our understanding of the mechanisms driving efficient autologous cell type conversion remains incomplete. Here, we evaluate a novel algorithmically predicted transcription factor (TF) recipe - GATA2, GFIB1, FOS, REL, and STAT5A - for inducing HSC-like states from human dermal fibroblasts. Using flow cytometry and long-read single-cell RNA-sequencing, we demonstrate increased CD34+cell populations and high transcriptomic similarity to native HSCs. Additionally, we uncover transcriptional heterogeneity at both gene and isoform levels among induced HSCs, underscoring the complexity of direct reprogramming.
Publisher
Cold Spring Harbor Laboratory