Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin

Abstract

The expression of CD10 has long been used to define human lymphoid commitment. We report a unique lymphoid-primed population in human bone marrow that was generated from hematopoietic stem cells (HSCs) before the onset of CD10 expression and B cell commitment. This subset was identified by high expression of the homing molecule L-selectin (CD62L). CD10−CD62Lhi progenitors possessed full lymphoid and monocytic potential, but lacked erythroid potential. Gene expression profiling placed the CD10−CD62Lhi population at an intermediate stage of differentiation between HSCs and lineage-negative (Lin−) CD34+CD10+ progenitors. L-selectin was expressed on immature thymocytes and its ligands were expressed at the cortico-medullary junction, suggesting a possible role in thymic homing. These studies identify the earliest stage of lymphoid priming in human bone marrow.

Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions

“…Fratalkine mediates leukocyte adhesion (Jones et al, 2010) and IL-10 is an anti-inflammatory cytokine (Braat et al, 2006). IP-10 and L-selectin attribute to diverse roles in neuroinflammation as well (Dufour et al, 2002;Kohn et al, 2012). Previous studies showed that AgNPs increased the permeability of brain microvessel endothelial cells through the release of proinflammatory mediators, which was responsible for AgNPs induced BBB inflammation (Trickler et al, 2010).…”

Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells

“…12,[20][21][22][23] However, as stated above, in addition to HSCs/MPPs, SRC activities were also found within LMPP fractions lacking erythro-myeloid differentiation potentials. 4,5 Furthermore, by comparing engraftment potentials of retrovirally marked baboon primitive haematopoietic cells in NOD/SCID mice and baboon, we previously provided evidence that cells other than true long term repopulating HSCs/MPPs are read out in the NOD/SCID xenotransplantation model. 24 Thus, documented expansion of SRC activity is not sufficient to claim expansion of multipotent HSCs/MPPs, unless the presence of human erythro-myeloid lineage-potentials has specifically been confirmed.…”

“…2 Later on, progenitors with LMPP characteristics were also detected in humans. [3][4][5] Dissecting the cell fate of different human progenitors including LMPPs by means of their CD133 and CD45RA expression, we provided evidence for novel lineage relationships within human haematopoiesis (Fig. 1A).…”

“…4,6 With regard to the revised model, functional in vivo analyses revealed that against the prevailing thinking HSCs/MPPs are not the only primitive progenitors with the capability to reconstitute NOD/SCID mice; LMPPs were also shown to engraft into NOD/SCID mice. 4,5 Since long-term human erythropoiesis is not supported 7 and analysis of human megakaryocytes as well as discrimination of granulocyte subtypes is commonly neglected in engrafted NOD/SCID mice, proof of erythro-myeloid potentials and thus multipotency of transplanted cells is lacking in many studies reporting expansion protocols of HSCs/MPPs. 8 Thus, the interpretation of several such studies has to be challenged.…”

Notch3 Activation Is Sufficient but Not Required for Inducing Human T-Lineage Specification

“…Although the precise identity of the human equivalent of mouse ETPs is still a matter of debate (34)(35)(36)(37), it is clear that the most immature human thymocytes reside within the CD34 + CD1a 2 population. We have previously shown that bulk CD34 + CD1a 2 thymocytes express both NOTCH1 and NOTCH3 mRNA (23) but now extend these results by investigating protein expression for Notch3 at the single-cell level using flow cytometry.…”