Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development

Inlay, Matthew A.; Bhattacharya, Deepta; Sahoo, Debashis; Serwold, Thomas; Seita, Jun; Karsunky, Holger; Plevritis, Sylvia K.; Dill, David L.; Weissman, Irving L.

doi:10.1101/gad.1836009

Cited by 271 publications

(378 citation statements)

References 29 publications

Supporting

Mentioning

345

Contrasting

Order By: Relevance

“…These factors set up a self-promoting feed-forward loop that establishes B-cell identity while eliminating differentiation into other affiliated cell lineages Rolink et al 1999;Pongubala et al 2008;Lin et al 2010;Treiber et al 2010;Nechanitzky et al 2013;Boller et al 2016). FOXO1 and EBF1 support each other's expression, while EBF1 also induces PAX5 that further augments EBF1 (Roessler et al 2007;Decker et al 2009;Inlay et al 2009;Mansson et al 2012).…”

Section: Lymphoid Lineage Commitment: An Ikaros Time Outmentioning

confidence: 99%

“…In a parallel process in the bone marrow, a subset of CLPs (also known as B lineage-restricted progenitors [BLPs]) under the influence of IL-7R signaling, E2A, and HEB induce expression of FOXO1 and EBF1 (Inlay et al 2009;Lin et al 2010;Welinder et al 2011). These factors set up a self-promoting feed-forward loop that establishes B-cell identity while eliminating differentiation into other affiliated cell lineages Rolink et al 1999;Pongubala et al 2008;Lin et al 2010;Treiber et al 2010;Nechanitzky et al 2013;Boller et al 2016).…”

Section: Lymphoid Lineage Commitment: An Ikaros Time Outmentioning

confidence: 99%

See 1 more Smart Citation

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

Georgopoulos

2017

Genes Dev.

View full text Add to dashboard Cite

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.

show abstract

Section: Lymphoid Lineage Commitment: An Ikaros Time Outmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

show abstract

“…The CLP compartment is heterogeneous, consisting of cells with different defined lineage potentials, as well as cells already committed to the B-cell fate. The CLP compartment can be segregated into two distinct populations based on the expression of the cell surface marker LY6D (4,5). During the last two decades, a subset of transcriptional regulators have been identified that specify and promote B-cell fate.…”

mentioning

confidence: 99%

Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

Månsson

Welinder

Åhsberg

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D + cell stage. We demonstrate that this phenotype closely resembles the arrest in B-cell development observed in EBF1-deficient mice. Consistent with these observations, we find that the transcription signatures of FOXO1-and EBF1-deficient LY6D + progenitors are strikingly similar, indicating a common set of target genes. Furthermore, we found that depletion of EBF1 expression in LY6D + CLPs severely affects FOXO1 mRNA abundance, whereas depletion of FOXO1 activity in LY6D + CLPs ablates EBF1 transcript levels. We generated a global regulatory network from EBF1 and FOXO1 genome-wide transcription factor occupancy and transcription signatures derived from EBF1-and FOXO1-deficient CLPs. This analysis reveals that EBF1 and FOXO1 act in a positive feedback circuitry to promote and stabilize specification to the B-cell lineage.

show abstract

“…for mature hematopoietic lineages. CD27 is expressed on HSCs and MPPs, and together with the red blood cell marker Ter119, can be used in place of Lin 14, 24, 25. Because this population (CD27+ Ter119– Kit+ Sca‐1+) is identical to the original KLS population (Lin‐ Kit+ Sca‐1+), we keep the nickname “KLS” for simplicity.…”

Section: Resultsmentioning

confidence: 99%

The CD11a and Endothelial Protein C Receptor Marker Combination Simplifies and Improves the Purification of Mouse Hematopoietic Stem Cells

Karimzadeh

Scarfone

Varady

et al. 2018

Stem Cells Translational Medicine

Self Cite

View full text Add to dashboard Cite

Hematopoietic stem cells (HSCs) are the self‐renewing multipotent progenitors to all blood cell types. Identification and isolation of HSCs for study has depended on the expression of combinations of surface markers on HSCs that reliably distinguish them from other cell types. However, the increasing number of markers required to isolate HSCs has made it tedious, expensive, and difficult for newcomers, suggesting the need for a simpler panel of HSC markers. We previously showed that phenotypic HSCs could be separated based on expression of CD11a and that only the CD11a negative fraction contained true HSCs. Here, we show that CD11a and another HSC marker, endothelial protein C receptor (EPCR), can be used to effectively identify and purify HSCs. We introduce a new two‐color HSC sorting method that can highly enrich for HSCs with efficiencies comparable to the gold standard combination of CD150 and CD48. Our results demonstrate that adding CD11a and EPCR to the HSC biologist's toolkit improves the purity of and simplifies isolation of HSCs. stem cells translational medicine 2018;7:468–476

show abstract

Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development

Cited by 271 publications

References 29 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

Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

The CD11a and Endothelial Protein C Receptor Marker Combination Simplifies and Improves the Purification of Mouse Hematopoietic Stem Cells

Contact Info

Product

Resources

About