Isolation of a candidate human hematopoietic stem-cell population.

TLDR

Human fetal bone marrow cells expressing Thy‑1 and CD34 without lineage markers are enriched for clonogenic activity that supports long‑term multilineage cultures on mouse stromal lines. We identified a rare (0.05–0.1%) Thy‑1⁺CD34⁺Lin⁻ fetal bone marrow population that is highly enriched for multipotent hematopoietic stem‑cell activity, capable of generating long‑term multilineage cultures, T cells in SCID mice, and donor‑derived myeloid and B cells, indicating it is a candidate HSC population.

Abstract

We have identified a rare (0.05-0.1%) subset of human fetal bone marrow cells that contains multipotent hematopoietic precursors. The population of human precursor cells that express Thy-1 and CD34 but no known lineage markers is enriched for clonogenic activity that establishes long-term, multilineage (myelomonocytic and B lymphoid) cultures on mouse marrow stromal lines. Further, the Thy-1+CD34+ subset that takes up little of the fluorescent mitochondrial dye rhodamine 123 contains virtually all the cells that establish long-term cultures. In human fetal thymus transplanted into SCID (severe combined immunodeficiency) mice, Thy-1+CD34+ fetal bone marrow cells differentiate into T lymphocytes. In two of nine cases, allogeneic Thy-1+CD34+ cells could engraft intact human fetal bone marrow grown in SCID mice, resulting in donor-derived myeloid and B cells. By extrapolation, the rare human Thy-1+Lin-CD34+ cell population contains pluripotent hematopoietic progenitors; we propose that it is highly enriched for candidate hematopoietic stem cells.