A human postnatal lymphoid progenitor capable of circulating and seeding the thymus

Six, Emmanuelle; Bonhomme, Delphine; Monteiro, Marta; Beldjord, Kheïra; Jurkowska, Monika; Cordier, Corinne; Garrigue, Alexandrine; Cortivo, Liliane Dal; Rocha, Bénédita; Fischer, Alain; Cavazzana‐Calvo, Marina; André-Schmutz, Isabelle

doi:10.1083/jcb1796oia18

Cited by 29 publications

(44 citation statements)

References 31 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to pre/pro-B-cell and pro-B-cell homogeneous Blineage profiles, only ∼1/20 of the individual CLP/early-B cells analyzed in parallel expressed Pax5, Rag-1, VpreB, or CD79a, and many did it in stochastic combinations of some of those genes. These findings, together with CD3ε or pre-Tα mRNA expression patterns in this population (8.3% and 12.3%, respectively), define CD34 + CD10 + CD19 − by phenotype and genotype as a CLP with a minor early-B-cell fraction (11,21). This is again similar to the findings reported for fresh CB counterparts (21).…”

Section: Cd19supporting

confidence: 79%

“…This is in agreement with the kinetics for the burst of conventional B-lineage development from fresh CB SCs or CLPs in other systems (17,18). Indeed, fresh CB CLPs (CD34 + CD10 int CD19 − ) developed into an early-B-committed intermediate (CD10 high CD19 − ) (11) and 45 ± 7% pro-B (CD10 high CD19 + ) cells after 21 days (yield of 146.3 ± 15-fold initial seeded cells) (Fig. S2B).…”

Section: Cd19supporting

confidence: 70%

“…In this pathway, CLP and early-B stages, which both express the CD34 + CD45RA + CD10 + CD19 − surface phenotype, are actually "multilineage" progenitors of B, T, dendritic (DC), and natural killer (NK) cells (5,(10)(11)(12).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Ordering human CD34⁺CD10⁻CD19⁺pre/pro-B-cell and CD19⁻common lymphoid progenitor stages in two pro-B-cell development pathways

Sanz

Muñoz-A.

Monserrat

et al. 2010

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

View full text Add to dashboard Cite

Studies here respond to two long-standing questions: Are human "pre/pro-B" CD34 + CD10 − CD19 + and "common lymphoid progenitor (CLP)/early-B" CD34 + CD10 + CD19 − alternate precursors to "pro-B" CD34 + CD19 + CD10 + cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig V H -D-J H sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34 high Lineage − pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34 + CD45RA + CD10 − CD19 − ) directly generate an initial wave of Pax5 + TdT − "unilineage" pre/ pro-B cells and a later wave of "multilineage" CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the V H -D-J H Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5 + TdT − pre/ pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway. Ordered stages in the current human model are termed the "common lymphoid progenitor" (CLP) and the "early-B," "progenitor-B," and "precursor-B" subsets that follow it (i.e., SC → CLP → early-B → pro-B → pre-B → B) (5). In this pathway, CLP and early-B stages, which both express the CD34 + CD45RA + CD10 + CD19 − surface phenotype, are actually "multilineage" progenitors of B, T, dendritic (DC), and natural killer (NK) cells (5, 10-12).Pro-B cells, which retain CD34 and CD10 expression but also express CD19 (CD34 + CD10 + CD19 + ), constitute the first Pax-5 + committed B-lineage stage, which is followed by pre-B (CD34 − CD10 + CD19 + ) cells that have ceased expression of CD34 and now express the surface μH-VpreB-λ5/CD79 surrogate Ig receptor complex (1-5, 13-15). Development of the latter CD34 − pre-B cells and their B-cell and Ig-secreting plasma cell progeny can be reconstituted after coculture of purified CD34 + Lineage − (Lin − ) progenitors with bone marrow (BM) stroma lines (e.g., S17) (15-18).Before the CLP subset and the above developmental pathway were recognized, a subset called "pre/pro-B," which expresses the CD34 + CD10 − CD19 + surface phenotype, was commonly considered to be the first human B-lineage stage (19). It occurs in fetal liver, fetal bone marrow (FBM), and umbilical cord blood (CB) (19-21). An FBM pre/pro-B cell stage was shown to distinctively lack TdT and to bear CD7 unlike concurrent conventional CD10 + CD19 − B-cell progenitors, leading to the idea that these cells might belong to a distinct B lineage (20). This lack of TdT-mediated "N-nucleotide additions" between D and J H segments is further associated with differential V-D-J gene...

show abstract

Section: Cd19supporting

confidence: 79%

Section: Cd19supporting

confidence: 70%

See 1 more Smart Citation

Ordering human CD34⁺CD10⁻CD19⁺pre/pro-B-cell and CD19⁻common lymphoid progenitor stages in two pro-B-cell development pathways

Sanz

Muñoz-A.

Monserrat

et al. 2010

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

View full text Add to dashboard Cite

show abstract

“…In humans, the phenotype of early progenitors is quite different from mice with the presence of CD34 and the absence of CD1a, a member of the CD1 family of MHC-like glycoproteins, defining the earliest progenitors. Recently, expression of the CD10 and CD24 markers has been shown to be associated with lymphoid differentiation potential; CD34þCD10þCD24À cells have the potential to generate B, T, and NK lineages but not myeloid lineage cells [43]. Nevertheless, it appears that this population of CLPs is skewed toward a B lymphocyte fate, whereas cord blood progenitors with a CD34þCD7þCD45RAþ phenotype express T/NK cell lineage-affiliated genes and show enhanced T lineage differentiation potential [44].…”

Section: Hematopoietic Precursor Differentiation Within the Thymusmentioning

confidence: 98%

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

2013

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell (HSC) transplantation can cure patients suffering from diverse genetic and acquired diseases as well as cancers. Nevertheless, under conditions where T-cell reconstitution is critical, the entry of donor progenitors into the thymus remains a major bottleneck. It is assumed that following the intravenous injection of HSC, they first home to the BM. More committed progenitors can then be exported to the thymus in response to a myriad of signals regulating thymus seeding. Notably although, the thymus is not continually receptive to the import of hematopoietic progenitors. Furthermore, as stem cells with self-renewing capacity do not take up residence in the thymus under physiological conditions, the periodic colonization of the thymus is essential for the sustained differentiation of T lymphocytes. As such, we and others have invested significant efforts into exploring avenues that might foster a long-term thymus-autonomous differentiation. Here, we review strategic approaches that have resulted in long-term T-cell differentiation in immunodeficient (SCID) mice, even across histocompatibility barriers. These include the forced thymic entry of BM precursors by their direct intrathymic injection as well as the transplantation of neonatal thymi. The capacity of the thymus to support hematopoietic progenitors with renewal potential will hopefully promote the development of new therapeutic strategies aimed at enhancing T-cell differentiation in patients undergoing HSC transplantation.

show abstract

“…CD10 was reported to mark early lymphoid committed cells present in bone marrow, blood, and thymus (20,21). We therefore analyzed whether CD10 ϩ cells could be detected in HZ.…”

Section: A Hesc-derived Cd34 High Cd43 Low Cell Population Generates mentioning

confidence: 99%

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Timmermans

Velghe

Vanwalleghem

et al. 2009

The Journal of Immunology

181

151

View full text Add to dashboard Cite

Human embryonic stem cells (hESC) are pluripotent stem cells. A major challenge in the field of hESC is the establishment of specific differentiation protocols that drives hESC down a particular lineage fate. So far, attempts to generate T cells from hESC in vitro were unsuccessful. In this study, we show that T cells can be generated in vitro from hESC-derived hematopoietic precursor cells present in hematopoietic zones (HZs). These zones are morphologically similar to blood islands during embryonic development, and are formed when hESC are cultured on OP9 stromal cells.

show abstract

A human postnatal lymphoid progenitor capable of circulating and seeding the thymus

Cited by 29 publications

References 31 publications

Ordering human CD34⁺CD10⁻CD19⁺pre/pro-B-cell and CD19⁻common lymphoid progenitor stages in two pro-B-cell development pathways

Ordering human CD34⁺CD10⁻CD19⁺pre/pro-B-cell and CD19⁻common lymphoid progenitor stages in two pro-B-cell development pathways

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Contact Info

Product

Resources

About

A human postnatal lymphoid progenitor capable of circulating and seeding the thymus

Cited by 29 publications

References 31 publications

Ordering human CD34+CD10−CD19+pre/pro-B-cell and CD19−common lymphoid progenitor stages in two pro-B-cell development pathways

Ordering human CD34+CD10−CD19+pre/pro-B-cell and CD19−common lymphoid progenitor stages in two pro-B-cell development pathways

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Contact Info

Product

Resources

About

Ordering human CD34⁺CD10⁻CD19⁺pre/pro-B-cell and CD19⁻common lymphoid progenitor stages in two pro-B-cell development pathways

Ordering human CD34⁺CD10⁻CD19⁺pre/pro-B-cell and CD19⁻common lymphoid progenitor stages in two pro-B-cell development pathways