[PDF][PDF] Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs
Cell stem cell, 2012•cell.com
Adult hematopoietic stem cells (HSCs) with serially transplantable activity comprise two
subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other
appears selectively lymphoid deficient. We now show that both of these HSC subtypes are
present in the fetal liver (at a 1: 10 ratio) with the rarer, lymphoid-deficient HSCs immediately
gaining an increased representation in the fetal bone marrow, suggesting that the marrow
niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis …
subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other
appears selectively lymphoid deficient. We now show that both of these HSC subtypes are
present in the fetal liver (at a 1: 10 ratio) with the rarer, lymphoid-deficient HSCs immediately
gaining an increased representation in the fetal bone marrow, suggesting that the marrow
niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis …
Summary
Adult hematopoietic stem cells (HSCs) with serially transplantable activity comprise two subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other appears selectively lymphoid deficient. We now show that both of these HSC subtypes are present in the fetal liver (at a 1:10 ratio) with the rarer, lymphoid-deficient HSCs immediately gaining an increased representation in the fetal bone marrow, suggesting that the marrow niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis of HSC expansion posttransplant showed that both subtypes display an extensive but variable self-renewal activity with occasional interconversion. Clonal analysis of their differentiation programs demonstrated functional and molecular as well as quantitative HSC subtype-specific differences in the lymphoid progenitors they generate but an indistinguishable production of multipotent and myeloid-restricted progenitors. These findings establish a level of heterogeneity in HSC differentiation and expansion control that may have relevance to stem cell populations in other hierarchically organized tissues.
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