Better understanding of how hematopoietic stem cells (HSCs) balance self-renewal and differentiation is vital for their efficient ex vivo maintenance and expansion and their application in treatment of various diseases and regenerative medicine. During the last decade, tremendous advances have been made in identifying a complex network of genes, pathways, and epigenetic factors that influence self-renewal and differentiation of HSCs and characterizing the cellular and molecular components of niches which harbor HSCs.

The mounting number of studies is also reporting the phenotypic, functional, and molecular heterogeneity of HSCs, which is not only arising from the coexistence of different HSC subsets, but also from HSCs alternating between several interconvertible states. These metastable states are characterized by distinct and alternating differentiation and by transcriptome and epigenetic patterns. These observations are shifting our perception of HSCs from being a functionally uniform pool to a dynamic pool of alternating cell subsets. The heterogeneity and metastability could enable HSCs to alternate between self-renewing states and states in which HSCs are both self-renewing and differentiating.

Improving our understanding of the cellular, molecular, and epigenetic mechanisms that affect and regulate the metastability, self-renewal, and differentiation of HSCs will have a profound impact on experimental and clinical HSC research and the use of HSCs in regenerative medicine. In addition, the studies of the reactivation/dysregulation of self-renewal in leukemic cells will be vital for better understanding of the origin and maintenance of leukemia initiating cells and their eradication. Potential topics include, but are not limited to:

• Phenotypic, functional, and molecular characterization of different HSC subsets
• The self-renewal and differentiation properties of different HSC subsets
• Molecular mechanisms enabling HSCs to balance self-renewal and differentiation
• Mechanism associated with and/or regulating HSC metastability
• Epigenetic and microRNA regulation of HSC self-renewal and differentiation
• Reactivation/dysregulation of self-renewal in leukemic transformation
• The role of BM niches in HSC heterogeneity, self-renewal, and differentiation
• The impact of hypoxia on HSC state and functional potency

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