Thymopoiesis independent of common lymphoid progenitors

Allman, David; Sambandam, Arivazhagan; Kim, Sungjune; Miller, Juli P.; Pagán, Antonio J.; Well, David; Meraz, Anita; Bhandoola, Avinash

doi:10.1038/ni878

Cited by 484 publications

(549 citation statements)

References 38 publications

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“…2; Allman et al 2003;Yoshida et al 2006). However, after lymphoid lineage potential is established in these progenitors, IKAROS is not required for further commitment into the T-cell or B-cell lineages (Fig.…”

Section: Lymphoid Lineage Commitment: An Ikaros Time Outmentioning

confidence: 99%

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma

Georgopoulos

2017

Genes Dev.

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Lymphocyte differentiation is set to produce myriad immune effector cells with the ability to respond to multitudinous foreign substances. The uniqueness of this developmental system lies in not only the great diversity of cellular functions that it can generate but also the ability of its differentiation intermediates and mature effector cells to expand upon demand, thereby providing lifelong immunity. Surprisingly, the goals of this developmental system are met by a relatively small group of DNA-binding transcription factors that work in concert to control the timing and magnitude of gene expression and fulfill the demands for cellular specialization, expansion, and maintenance. The cellular and molecular mechanisms through which these lineage-promoting transcription factors operate have been a focus of basic research in immunology. The mechanisms of development discerned in this effort are guiding clinical research on disorders with an immune cell base. Here, I focus on IKAROS, one of the earliest regulators of lymphoid lineage identity and a guardian of lymphocyte homeostasis.

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Section: Lymphoid Lineage Commitment: An Ikaros Time Outmentioning

confidence: 99%

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma

Georgopoulos

2017

Genes Dev.

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“…This model was supported by the prospective isolation of cell populations with CLP and CMP function from the murine BM. 1,2 Recent evidence, however, indicated that BM CLPs are not physiological T-cell progenitors, as early thymic progenitors (ETPs) do not have the CLP phenotype 3 and CLPs are not present in the peripheral blood. 4 Instead, the thymus is most likely seeded by a multipotent progenitor.…”

Section: Introductionmentioning

confidence: 99%

T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34+CD38−CD7+ common lymphoid progenitors expressing lymphoid-specific genes

et al. 2006

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Hematopoietic stem cells in the bone marrow (BM) give rise to all blood cells. According to the classic model of hematopoiesis, the differentiation paths leading to the myeloid and lymphoid lineages segregate early. A candidate 'common lymphoid progenitor' (CLP) has been isolated from CD34 þ CD38 À human cord blood cells based on CD7 expression. Here, we confirm the B-and NK-differentiation potential of CD34 þ CD38 À CD7 þ cells and show in addition that this population has strong capacity to differentiate into T cells. As CD34 þ CD38 À CD7 þ cells are virtually devoid of myeloid differentiation potential, these cells represent true CLPs. To unravel the molecular mechanisms underlying lymphoid commitment, we performed genome-wide gene expression profiling on sorted CD34 þ CD38 À CD7 þ and CD34 þ CD38 À CD7 À cells. Interestingly, lymphoid-affiliated genes were mainly upregulated in the CD7 þ population, while myeloid-specific genes were downregulated. This supports the hypothesis that lineage commitment is accompanied by the shutdown of inappropriate gene expression and the upregulation of lineage-specific genes. In addition, we identified several highly expressed genes that have not been described in hematopoiesis before.

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“…The earliest lymphocyte progenitor (ELP; Igarashi et al 2002) and later common lymphoid progenitor (CLP; Allman et al 2003) already initiate D H -J H rearrangements, which are completed during development to the early pro-B-cell stage (fraction B; Li et al 1993). As the ELP and CLP also give rise to T, NK, and dendritic cells (Kondo et al 1997;Traver et al 2000;Igarashi et al 2002), it may not be surprising that these cell types carry D H -J H -rearranged IgH alleles at low frequency (Kurosawa et al 1981;Born et al 1988;Corcoran et al 2003).…”

mentioning

confidence: 99%

Pax5 inducesV-to-DJrearrangements and locus contraction of theimmunoglobulin heavy-chaingene

Fuxa¹,

Skok²,

Souabni³

et al. 2004

Genes Dev.

372

457

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Thymopoiesis independent of common lymphoid progenitors

Cited by 484 publications

References 38 publications

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma

T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34+CD38−CD7+ common lymphoid progenitors expressing lymphoid-specific genes

Pax5 inducesV-to-DJrearrangements and locus contraction of theimmunoglobulin heavy-chaingene

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