Methods for purifying very small embryonic-like (VSEL) stem cells from populations of cells suspected of including VSEL stem cells are provided. In some embodiments, the methods include (a) providing a population of cells suspected of including a VSEL stem cell and (b) isolating a CD45neg/GlyAneg/CD133+/ALDHhigh subpopulation, a CD45neg/GiyAneg/CD133+/ALDlow subpopulation, a CD45neg/Linneg/SSEA-4+/ALDHhigh subpopulation, a CD45neg/Linneg/SSEA-4/AiOlow subpopulation, or any combination thereof from the population, whereby a VSEL stem cell is purified from the population. Also provided are methods for generating in vitro hematopoietic colonies derived from VSEL stem cells and methods for generating lympho-hematopoietic chimerism in a subject.