The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs with genetic barcodes, allowing clonal tracking over time and space after transplantation. We found marked geographic segregation of CD34⁺ HSPCs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at different BM sites over subsequent months to years. Clonal mapping was used to document local production of granulocytes, monocytes, B cells, and CD56⁺ natural killer (NK) cells. In contrast, CD16⁺CD56⁻ NK cells were not produced in the BM, and in fact were clonally distinct from multipotent progenitors producing all other lineages. Most surprisingly, we documented local BM production of CD3⁺ T cells early after transplantation, using both clonal mapping and intravascular versus tissue-resident T cell staining, suggesting a thymus-independent T cell developmental pathway operating during BM regeneration, perhaps before thymic recovery.

在了解克隆过程中造血干细胞和祖细胞（HSPC）及其后代与骨髓（BM）壁how如何相互作用的过程中，造血细胞在克隆水平上的地理分布很有意义。我们用遗传条形码标记恒河猴自体HSPC，从而在移植后随时间和空间进行克隆追踪。我们发现，在移植后至少6个月内，CD34 ⁺ HSPC出现了明显的地理隔离，随后在接下来的数月至数年中，在不同的BM部位进行了非常缓慢的克隆混合。克隆作图用于记录粒细胞，单核细胞，B细胞和CD56 ⁺自然杀伤（NK）细胞的局部产生。相比之下，CD16 ⁺ CD56 ^-NK细胞不是在BM中产生的，实际上在克隆方面不同于产生所有其他谱系的多能祖细胞。最令人惊讶的是，我们使用克隆作图以及血管内和组织内T细胞染色记录了移植后早期CD3 ⁺ T细胞的局部BM产生，这表明在BM再生期间，也许在胸腺恢复之前，胸腺非依赖性T细胞发育途径起作​​用。