Clonal analysis of fetal hematopoietic stem/progenitor cell subsets reveals how post-transplantation capabilities are distributed

• DOI: 10.1101/2024.02.19.579920
• Publication Date: 2024-02-20T03:15:18Z
• Authors: Olivia Stonehouse; Christine Biben; Tom S Weber; Alexandra Garnham; Katie Fennell; Alison Farley; Antoine Terreaux; Warren Alexander; Mark Dawson; Shalin Naik; Samir Taoudi
• Keywords: Immunophenotyping; Lineage (genetic)

It has been proposed that adult haematopoiesis is sustained by multipotent progenitor (MPP) clones are specified during development. From an immunophenotypic perspective, it known hematopoietic stem cell (HSC) and MPPs present in the fetal liver yet our understanding of how functionally compare to those bone marrow incomplete. Using acute-term transplantations, we found at a population-level MPP classes exhibited similar lineage biases as cells, albeit with some difference lymphoid output. Clonal assessment engraftment revealed largely resulted from differences pattern single- or bi-lineage differentiation. Immunophenotypic long-term (LT)- short-term (ST)-HSCs were distinguished according propensity for clonal multi-lineage We also discovered large cohort repopulating units (LT-RU) within ST-HSC population, significant portion these labelled using Flt3-cre. This finding two implications: (1) use CD150+ LT-HSC immunophenotype alone will systematically underestimate size diversity LT-RU pool; and, (2), given LT-RUs have functional attributes required persist into adulthood.