L-selectin defines a bone marrow analog to the thymic early T-lineage progenitor

Perry, S. Scott; Wang, Hongfang; Pierce, Lauren; Yang, Anne Marie; Tsai, Schickwann; Spangrude, Gerald J.

doi:10.1182/blood-2003-09-3030

Cited by 88 publications

(88 citation statements)

References 46 publications

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“…Similarly, injection of 2 Â 10 4 freshly isolated EPLM transiently reconstituted the thymus and BM of irradiated RAG-2 recipients. No detectable myeloid reconstitution by EPLM was seen in vivo, reflecting the difficulty of efficiently reconstituting the myeloid lineage in vivo [21]. EPLM could also efficiently give rise to T cells in vitro when cultured on OP9-DL1 stroma in the presence of IL-7 or when transferred into FTOC.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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Section: Discussionmentioning

confidence: 99%

“…Reconstitution of TCRb + DP cells in the thymus and of the precursor B cell compartment in the BM was detected only transiently and had disappeared by 5 wk [21], was more difficult than revealing their T and B cell potential. …”

Section: Single Cells Can Give Rise To Both T and B Cellsmentioning

confidence: 99%

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

et al. 2005

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“…In mice, multipotent progenitors (MPP), retaining both myeloid and lymphoid potential, are generated from HSC and are characterized by the upregulation of the Fms-like tyrosine kinase receptor 3 (Flt3/CD135; resulting in LSK/CD135þ cells) [36]. Subsets of MPP, characterized by expression of molecules such as RAG-1 [37] and Lselectin [38], can also give rise to thymic precursors. Common lymphocyte precursors (CLPs) are more committed in that they lack myeloid potential and these progenitors can be distinguished as CLP-1 (Lin-Sca-1þCD117þ/loCD127þCD135þ) [39] and CLP-2 (Lin-Sca-1þCD117-CD127þCD135þB220þ) [40].…”

Section: Hematopoietic Precursor Differentiation Within the Thymusmentioning

confidence: 99%

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

2013

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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.

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“…or intrathymic transplant (12,13); however, cells with stem cell properties have not been found in the thymus (8,11,14,15). This observation and the fact that other marrow fractions can more rapidly seed the thymus under experimental conditions suggest that HSC are not directly responsible for maintaining thymocytopoiesis (12,16). Our focus was on testing marrow cells that rapidly generate large numbers of thymocytes, and on assessing the loss of other differentiation options.…”

mentioning

confidence: 99%

“…Furthermore, a consensus has developed that these early thymic progenitors (ETP) express high levels of c-Kit (9,24,33,34). The primitive c-Kit high ETP are uniformly L-selectin ϩ (16,35), and regenerating thymocytes in irradiated mice are initially Thy1 Ϫ (13). As noted here, ETP express little IL-7R␣, but all are Sca1 ϩ , and ones that retain some B potential are Flt3/Flk-2 ϩ (3,14,15,24,33,36).…”

mentioning

confidence: 99%

Primitive Lymphoid Progenitors in Bone Marrow with T Lineage Reconstituting Potential

Perry

Welner

Kouro

et al. 2006

The Journal of Immunology

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Multiple subsets of the bone marrow contain T cell precursors, but it remains unclear which is most likely to replenish the adult thymus. Therefore, RAG-1+ early lymphoid progenitors (RAG-1+ ELP), and CD62L/L-selectin+ progenitors (LSP), as well as common lymphoid progenitors from C57BL6-Thy1.1-RAG-1/GFP mouse bone marrow were directly compared in transplantation assays. The two c-Kithigh populations vigorously regenerated the thymus and were superior to common lymphoid progenitors in magnitude and frequency of thymic reconstitution. Regeneration was much faster than the 22 days described for transplanted stem cells, and RAG-1+ ELP produced small numbers of lymphocytes within 13 days. As previously reported, LSP were biased to a T cell fate, but this was not the case for RAG-1+ ELP. Although RAG-1+ ELP and LSP had reduced myeloid potential, they were both effective progenitors for T lymphocytes and NK cells. The LSP subset overlapped with and included most RAG-1+ ELP and many RAG-1−TdT+ ELP. LSP and RAG-1+ ELP were both present in the peripheral circulation, but RAG-1+ ELP had no exact counterpart among immature thymocytes. The most primitive of thymocytes were similar to Lin−c-KithighL-selectin+TdT+RAG-1− progenitors present in the marrow, suggesting that this population is normally important for sustaining the adult thymus.

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L-selectin defines a bone marrow analog to the thymic early T-lineage progenitor

Cited by 88 publications

References 46 publications

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

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

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

Primitive Lymphoid Progenitors in Bone Marrow with T Lineage Reconstituting Potential

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