Historical sequence of methods used to detect and quantify mouse HSCs in vivo. (A) Development of LDA approaches to identify the transplantable cells that can rescue mice permanently from radiation-induced lethality by regenerating the inactivated blood-forming system of the host. (B) Genetic approaches to track HSCs by detection of their long-lived clonal outputs in transplanted recipients. Random sites of vector integration into the DNA of the regenerated progeny of transduced transplanted cells were the first unique DNA identifiers used.^3,4  More recently, uptake of a single vector encoding a short unique “barcode” sequence from a diverse vector library has been used as a clonal tracking strategy.^94-97  (C) Advances in LTRC purification enabling single-cell transplants to reveal the diversity of long-term clonal white blood cell outputs of individual HSCs as previously suggested by limiting dilution transplants and vector-marking experiments. Data shown are for purified Rho⁻SP⁺ LTRCs (HSCs) adapted from Uchida et al⁵  (with permission from Experimental Hematology.) BM, bone marrow; L+M, lymphoid + myeloid; mo, months; LAM-PCR, linear amplification mediated polymerase chain reaction; SP, side population; UV, ultraviolet; WBCs, white blood cells.