Tracing the first waves of lymphopoiesis in mice

Abstract

RAG1/GFP knock-in mice were used to precisely chart the emergence and expansion of cells that give rise to the immune system. Lymphopoietic cells detectable in stromal co-cultures arose as early as E8.5, i.e. prior to establishment of the circulation within the paraaortic splanchnopleura (P-Sp). These cells were Tie2While yolk sac (YS) also contained lymphopoietic cells after E9.5, CD41+ YS cells from р25-somite embryos produced myelo-erythroid cells but no lymphocytes. Notch receptor signaling directed P-Sp cells to T lymphocytes but did not confer lymphopoietic potential on YS cells. Thus, definitive hematopoiesis arises in at least two independent sites that differ in lymphopoietic potential. Expression of RAG1, the earliest known lymphoid event, first occurred around E10.5 within the embryos. RAG1/GFP + cells appeared in the liver at E11.0 and progenitors with B and/or T lineage potential were enumerated at subsequent developmental stages.

Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo

“…+ yolk sac cells generate multiple myeloid and erythroid lineages, but lack lymphoid potential in co-culture assays (Yokota et al, 2006). Similar results were obtained at E10.5 using yolk sac cells purified by combined CD41 + c-Kit + CD45 -expression (Bertrand et al, 2005b).…”

“…It is widely believed that definitive hematopoiesis subsequently begins in the midgestation embryo with the formation of HSCs in a region bounded by the aorta, gonads and mesonephros (AGM) (Dzierzak, 2005;Cumano and Godin, 2007). However, recent studies have demonstrated the presence of definitive progenitors within the yolk sac (Yoder et al, 1997a;Yoder et al, 1997b;Palis et al, 1999;Bertrand et al, 2005a;Yokota et al, 2006;Yokomizo et al, 2007) and placenta (Gekas et al, 2005;Ottersbach and Dzierzak, 2005;Zeigler et al, 2006) that arise either before, or concomitant with, HSC formation in the AGM region. Several reports have shown that a common marker of definitive hematopoietic stem and progenitor cells in each of these tissues is the integrin, CD41 (Mitjavila-Garcia et al, 2002;Ferkowicz et al, 2003;Mikkola et al, 2003;Ottersbach and Dzierzak, 2005).…”

Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling

“…Mint Ϫ/Ϫ mice used in the present study survive until E14.5, and they die soon after E16 because of cardiovascular defects with severe s.c. edema. Lymphoid progenitors begin to immigrate to the thymus around E11.5 (38,39). Although few double-positive (DP) and single-positive (SP) cells were found at this stage of embryonic thymus, DN cells were clearly identified.…”

Markers for Hematopoietic Stem Cells: Histories and Recent Achievements

“…Therefore, it seems quite natural that HSC share some surface molecules with the endothelial lineage. CD34, PECAM-1/CD31, endoglin, Tie2 and VE-cadherin are well-known endothelial antigens that also mark HSC particularly at early developmental stages (Mikkola & Orkin 2006;Takakura et al, 1998;Yokota et al, 2006). In addition, recent studies have identified endomucin, endothelial protein-C receptor/CD201, and junctional adhesion molecule-A that are common to HSC and endothelial cells (Matsubara et al, 2005;Balazs et al, 2006;Sugano et al, 2008).…”

“…We previously determined that, while myelo-erythroid progenitors emerge from the yolk sac, hematopoietic progenitors with lymphopoietic potential first develop in the paraaortic splanchnopleura (pSp) /AGM region (Yokota et al, 2006). ESAM + cells in the AGM were found to co-express c-kit and endothelial antigens, Tie2, CD34 and CD31/PECAM-1 that are known as a marker set for emerging HSC.…”