A B220+ CD117+ CD19± hematopoietic progenitor with potent lymphoid and myeloid developmental potential

Balc̆iūnaite, Gina; Ceredig, Rhodri; Massa, Steffen; Rolink, Antonius

doi:10.1002/eji.200526318

Cited by 132 publications

(168 citation statements)

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“…Recently, we identified in the bone marrow of wild-type mice a B220 + c-kit + CD19 -NK1.1 -cell, which we termed EPLM, and which posses the potential to give rise to T and B cells in vitro and in vivo [10]. Thus, EPLM cultured on OP9 in the presence of IL-7 gave rise to B cell progenitors, while the same cells cultured on OP9-DL1 in the presence of IL-7 differentiated into T lineage cells.…”

Section: The Differentiation Of Eplm Into the T But Not B Cell Lineagmentioning

confidence: 99%

“…They showed that hematopoietic stem cells cultured on OP9 stromal cells expressing the Notch ligand delta-like-1 (DL1) differentiated along the T cell lineage, whereas when cultured on the non-DL1-expressing OP9 they give rise to B cells. Using these OP9, OP9-DL1 culture systems, we have recently identified in the bone marrow of adult wild-type mice, a B220 + c-kit + CD19 -NK1.1 -cell, called early progenitors with lymphoid and myeloid potential (EPLM), which efficiently give rise to T and B lineage cells [10]. Phenotypically and functionally, EPLM shared many properties with Pax5-deficient progenitor B (Pax5 -/-pro-B) cells.…”

Section: Introductionmentioning

confidence: 99%

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Critical role for c‐kit (CD117) in T cell lineage commitment and early thymocyte development in vitro

Massa¹,

Balc̆iūnaite²,

Ceredig³

et al. 2006

Eur J Immunol

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The precise roles played by the transmembrane receptor tyrosine kinase c-kit and its ligand stem cell factor in early T cell development are difficult to study. Using cloned Pax5-deficient progenitor B cells, we show that following Notch signaling, which induces their commitment to the T cell developmental pathway, c-kit expression is rapidly up-regulated at both the transcriptional and cell surface level. Using either an anti-c-kit monoclonal antibody or Gleevec, a pharmacological inhibitor of c-kit signaling, we show that the Notch-induced T cell differentiation of either Pax5-deficient progenitor B cells, or the equivalent cell from the bone marrow of normal mice, is strictly dependent on c-kit signaling, whereas the differentiation of normal progenitors into the B cell lineage is not. Moreover, we show that the Notch and IL-7 signalinginduced proliferation and differentiation of CD44 + CD25 -c-kit high and CD44 + CD25 + ckit high thymocytes along the T cell, but not natural killer cell or macrophage, pathway also requires c-kit signaling, whereas the Notch-induced proliferation and differentiation of CD44 -CD25 + c-kit int cells along the T cell pathway is independent of c-kit. These results further highlight the complex inter-relationships existing between c-kit, Notch and IL-7 receptor signaling that control the proliferation and differentiation of early T cell progenitors.

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Section: The Differentiation Of Eplm Into the T But Not B Cell Lineagmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Critical role for c‐kit (CD117) in T cell lineage commitment and early thymocyte development in vitro

Massa¹,

Balc̆iūnaite²,

Ceredig³

et al. 2006

Eur J Immunol

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“…Similar to common lymphoid progenitors (CLP), EPLM have T cell, B cell but also myeloid potential, and these cells appear to usually travel down the B cell pathway [15]. Progenitors with such potential could be considered 'B cell biased' but not B cell-committed.…”

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confidence: 99%

“…are 'B cell biased'). A well-characterized example of this cell type is the early progenitor with lymphoid and myeloid potential (EPLM) [15]. Once in the thymus, the different progenitors can be identified at high resolution according to cell surface markers (CD3, CD4, CD8 [triple negative; TN], CD117 [c-Kit], CD24, CD44, CD25, not indicated).…”

mentioning

confidence: 99%

“…[16,17] and reviewed in [18]). These include (A) cells with a bone marrow hematopoietic stem cell (HSC)-like phenotype (KLS) expressing high levels of c-Kit [19] or (B) common lymphoid progenitor (CLP)-like phenotypes ( [15,20,21] and reviewed in [22]). KLS are generally considered multipotent cells but the multipotency, in particular the B cell potential, of the earliest intrathymic progenitors is controversial.…”

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Making a Notch in the lymphocyte kit

Rodewald

2006

Eur J Immunol

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The receptor tyrosine kinase c-Kit plays crucial roles in lymphocyte development but there is little information on the molecular circuitry enforcing c-Kit expression. In addition to growth factors, Notch signaling is essential for T cell development. In this issue of the European Journal of Immunology, evidence is provided for an interesting link between c-Kit and Notch. The primary 'test subjects' were a Pax5-deficient 'pro-B cell' line, blocked in its B cell potential, and its non-mutated counterpart, a bone marrowderived early progenitor with lymphoid and myeloid potential (EPLM). Similar to common lymphoid progenitors, EPLM have a 'B cell-biased' potential, yet show multipotency under appropriate conditions. Following Notch signaling, c-Kit expression was very rapidly upregulated and the development into T cells was found to be c-Kitdependent. In the absence of Notch signals, c-Kit expression remained low. Development into non-T cell fates (NK or myeloid) was found to be c-Kit-independent. It remains to be determined whether c-Kit is a 'direct' target of the Notch signal transduction pathway; however, these findings, together with those of others, strongly suggest that Notch can contribute to the proper cytokine receptor pattern required for commitment and expansion of early intrathymic progenitors. Cytokines are not only crucial for the regulation of peripheral immune functions but also for the continuous development of hematopoietic cells. In the case of T lymphocytes, two growth factor receptors, the receptor tyrosine kinase c-Kit, and the interleukin 7 receptor (IL-7R), play crucial roles in the expansion and differentiation of progenitor thymocytes (reviewed in [1]). The requirements for signaling via these two receptors are modulated during ontogeny. Up to the fetal and neonatal stages, T cell development is severely reduced but permissive in mice lacking only c-Kit expression (c-Kit W/W ; 'W' for white spotted [2]) or only IL-7R expression, but is completely blocked in doubledeficient mice [3]. This suggests that c-Kit and IL-7R act synergistically during the initial establishment of the T cell compartment. Analysis of the role of c-Kit in adult mice was, for a long time, hampered by the fact that mice homozygous for the natural c-Kit W allele die in the neonatal period [2] owing to severe anemia; however, this defect can be selectively compensated for by transgenic overexpression of erythropoietin [4]. Analyses of these 'W-rescued by epo' ('Wepo') mice has Because of this marked paucity of lymphocyte progenitors in adult c-Kit W/W mice, it has been very difficult to analyze the role of c-Kit in lymphocyte development at the molecular level. As a result, until recently, there was very little information on the signals emanating from c-Kit in early thymocytes; however, the recent generation and analysis of mouse mutants with single amino acid substitutions in c-Kit has revealed the importance of tyrosine 567 in its cytoplasmic tail pointing to a crucial role for this Src binding site in lymphocyte pro...

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Acute leukemia of ambiguous lineage, not otherwise specified with FLT3‐ITD mutation and a possible origin in the common lymphoid progenitor

Martin‐Moro

2023

Cytometry Part B Clinical

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A B220+ CD117+ CD19± hematopoietic progenitor with potent lymphoid and myeloid developmental potential

Cited by 132 publications

References 31 publications

Critical role for c‐kit (CD117) in T cell lineage commitment and early thymocyte development in vitro

Critical role for c‐kit (CD117) in T cell lineage commitment and early thymocyte development in vitro

Making a Notch in the lymphocyte kit

Acute leukemia of ambiguous lineage, not otherwise specified with FLT3‐ITD mutation and a possible origin in the common lymphoid progenitor

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