Hematopoietic stem cells (HSCs) are characterized by their unique function to produce all lineages of blood cells throughout life. Such tissue‐specific function of HSC is attributed to their ability to execute self‐renewal and multilineage differentiation. Accumulating evidence indicates that the undifferentiated state of HSC is characterized by dynamic maintenance of chromatin structures and epigenetic plasticity. Conversely, quiescence, self‐renewal, and differentiation of HSCs are dictated by complex regulatory mechanisms involving specific transcription factors and microenvironmental crosstalk between stem cells and multiple compartments of niches in bone marrows. Thus, multidimensional regulatory inputs are integrated into two opposing characters of HSCs—maintenance of undifferentiated state analogous to pluripotent stem cells but execution of tissue‐specific hematopoietic functions. Further studies on the interplay of such regulatory forces as “cell fate determinant” will likely shed the light on diverse spectrums of tissue‐specific stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.