The evolution of hematopoietic models through a clonal lens

Area of Science:

• Hematology
• Stem Cell Biology
• Immunology

Background:

• Haematopoiesis is a regulated process where stem cells produce blood cells.
• Understanding haematopoietic stem cell (HSC) commitment is vital for cell therapy.
• Current knowledge gaps exist in predicting lineage fate and in vivo processes.

Purpose of the Study:

• To review conceptual frameworks of haematopoiesis.
• To highlight the role of clonal lineage-tracing and multi-omics.
• To discuss computational models and future challenges in haematopoiesis research.

Main Methods:

• Review of existing literature on haematopoiesis models.
• Analysis of data from clonal lineage-tracing studies (mouse, primate, human).
• Discussion of computational modeling approaches.

Main Results:

• Evidence supports predetermined lineage fate over stochastic acquisition.
• Clonal multi-omics approaches are key to identifying fate predictors.
• Various models, from discrete hierarchy to continuous and multi-track, have been proposed.

Conclusions:

• A clonal perspective is essential for identifying molecular signatures that predict cell fate.
• Further research is needed to resolve in vivo haematopoiesis and disease-related alterations.
• Understanding these mechanisms can advance in vitro and in vivo cell therapy applications.