Publications by authors named "Christophe Lancrin"

18 Publications

  • Page 1 of 1

MOF Histone Acetyltransferase in Blood Cell Development.

Trends Genet 2020 09 3;36(9):632-634. Epub 2020 Jul 3.

EMBL Rome - Epigenetics and Neurobiology Unit, Via Ramarini 32, 00015 Monterotondo, Italy. Electronic address:

Gene expression is regulated by transcription factors (TFs) and chromatin modifiers such as histone acetyltransferases (HATs). Pessoa Rodrigues et al. revealed the role of the Males absent on the first (MOF) HAT in hematopoietic stem cell (HSC) differentiation into red blood cells. This work raises interesting questions about how MOF controls other hematopoietic differentiation processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tig.2020.06.010DOI Listing
September 2020

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition.

Nat Commun 2020 Jan 29;11(1):586. Epub 2020 Jan 29.

European Molecular Biology Laboratory, EMBL Rome - Epigenetics and Neurobiology Unit, via E. Ramarini 32, 00015, Monterotondo, Italy.

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening, we identify CD44 as a marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros (AGM) region. This allows us to provide a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which HSPCs emerge. They are characterized with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists, a downregulation of genes related to glycolysis and the TCA cycle, and a lower rate of cell cycle. Moreover, we demonstrate that by inhibiting the interaction between CD44 and its ligand hyaluronan, we can block EHT, identifying an additional regulator of HSPC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-14171-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989687PMC
January 2020

Iron deficiency disrupts embryonic haematopoiesis but not the endothelial to haematopoietic transition.

Sci Rep 2019 04 23;9(1):6414. Epub 2019 Apr 23.

European Molecular Biology Laboratory, EMBL Rome, Epigenetics and Neurobiology Unit, Via Ramarini 32, 00015, Monterotondo, Italy.

In this study, we aimed to explore how cellular iron status affects embryonic haematopoiesis. For this purpose, we used a model of mouse embryonic stem cell differentiation into embryonic haematopoietic progenitors. We modulated the iron status by adding either the iron chelator Deferoxamine (DFO) for iron deficiency, or ferric ammonium citrate for iron excess, and followed the emergence of developing haematopoietic progenitors. Interestingly, we found that iron deficiency did not block the endothelial to haematopoietic transition, the first step of haematopoiesis. However, it did reduce the proliferation, survival and clonogenic capacity of haematopoietic progenitors. Surprisingly, iron deficiency affected erythro-myeloid progenitors significantly more than the primitive erythroid ones. Erythro-myeloid progenitors expressed less transferrin-receptor on the cell surface and had less labile iron compared to primitive erythroid progenitors, which could reduce their capacity to compete for scarce iron and survive iron deficiency. In conclusion, we show that iron deficiency could disturb haematopoiesis at an early embryonic stage by compromising more severely the survival, proliferation and differentiation of definitive haematopoietic progenitors compared to restricted erythroid progenitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-42765-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478831PMC
April 2019

Quantification of Mouse Hematopoietic Progenitors' Formation Using Time-lapse Microscopy and Image Analysis.

Bio Protoc 2019 01;9(1)

European Molecular Biology Laboratory, EMBL Rome, Epigenetics and Neurobiology Unit Monterotondo, Italy.

differentiation of mouse embryonic stem cells (mESCs) towards blood cells constitutes a well-established system to study the endothelial-to-hematopoietic transition (EHT) at the onset of blood development. Assessing the emergence of small non-adherent round blood cells in the culture without disturbing it is essential to evaluate the progression of EHT and also to test conditions potentially enhancing or repressing this process. Here, we describe how to quantify the formation of mouse hematopoietic progenitors during EHT in normal conditions or following over-expression of eight essential transcription factors using time-lapse microscopy and image analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21769/BioProtoc.3137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331043PMC
January 2019

Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis.

Elife 2018 03 20;7. Epub 2018 Mar 20.

European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy.

Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers. Within the heptad, we identified two sets of factors of opposing functions: one (Erg/Fli1) promoting the endothelial cell fate, the other (Runx1/Gata2) promoting the hematopoietic fate. Surprisingly, our data suggest that even though Fli1 initially supports the endothelial cell fate, it acquires a pro-hematopoietic role when co-expressed with Runx1. This work demonstrates the power of single-cell RNA-sequencing for characterizing complex transcription factor dynamics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.29312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860872PMC
March 2018

Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium.

Development 2018 03 12;145(5). Epub 2018 Mar 12.

Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation. The use of inducible expression combined with alterations in the expression of the RUNX1 co-factor CBFβ allowed us to evaluate a wide range of RUNX1 levels. We demonstrate that low RUNX1 levels are sufficient and necessary to initiate an effective endothelial-to-hematopoietic transition. Subsequently, RUNX1 is also required to complete the endothelial-to-hematopoietic transition and to generate functional hematopoietic precursors. In contrast, elevated levels of RUNX1 are able to drive an accelerated endothelial-to-hematopoietic transition, but the resulting cells are unable to generate mature hematopoietic cells. Together, our results suggest that RUNX1 dosage plays a pivotal role in hemogenic endothelium maturation and the establishment of the hematopoietic system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.149419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868988PMC
March 2018

Activation of the TGFβ pathway impairs endothelial to haematopoietic transition.

Sci Rep 2016 Feb 19;6:21518. Epub 2016 Feb 19.

European Molecular Biology Laboratory, Mouse Biology Unit, Via Ercole Ramarini 32, 00015 Monterotondo, Italy.

The endothelial to haematopoietic transition (EHT) is a key developmental process where a drastic change of endothelial cell morphology leads to the formation of blood stem and progenitor cells during embryogenesis. As TGFβ signalling triggers a similar event during embryonic development called epithelial to mesenchymal transition (EMT), we hypothesised that TGFβ activity could play a similar role in EHT as well. We used the mouse embryonic stem cell differentiation system for in vitro recapitulation of EHT and performed gain and loss of function analyses of the TGFβ pathway. Quantitative proteomics analysis showed that TGFβ treatment during EHT increased the secretion of several proteins linked to the vascular lineage. Live cell imaging showed that TGFβ blocked the formation of round blood cells. Using gene expression profiling we demonstrated that the TGFβ signalling activation decreased haematopoietic genes expression and increased the transcription of endothelial and extracellular matrix genes as well as EMT markers. Finally we found that the expression of the transcription factor Sox17 was up-regulated upon TGFβ signalling activation and showed that its overexpression was enough to block blood cell formation. In conclusion we showed that triggering the TGFβ pathway does not enhance EHT as we hypothesised but instead impairs it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep21518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759586PMC
February 2016

GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1.

Nat Cell Biol 2016 Jan 30;18(1):21-32. Epub 2015 Nov 30.

CRUK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.

In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta-gonad-mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothelial-to-haematopoietic transition (EHT). Here, we establish the absolute requirement of the transcriptional repressors GFI1 and GFI1B (growth factor independence 1 and 1B) in this unique trans-differentiation process. We first demonstrate that Gfi1 expression specifically defines the rare population of HE that generates emerging HSCs. We further establish that in the absence of GFI1 proteins, HSCs and haematopoietic progenitor cells are not produced in the AGM, revealing the critical requirement for GFI1 proteins in intra-embryonic EHT. Finally, we demonstrate that GFI1 proteins recruit the chromatin-modifying protein LSD1, a member of the CoREST repressive complex, to epigenetically silence the endothelial program in HE and allow the emergence of blood cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncb3276DOI Listing
January 2016

GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment.

Blood 2012 Jul 5;120(2):314-22. Epub 2012 Jun 5.

Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.

Recent studies have established that during embryonic development, hematopoietic progenitors and stem cells are generated from hemogenic endothelium precursors through a process termed endothelial to hematopoietic transition (EHT). The transcription factor RUNX1 is essential for this process, but its main downstream effectors remain largely unknown. Here, we report the identification of Gfi1 and Gfi1b as direct targets of RUNX1 and critical regulators of EHT. GFI1 and GFI1B are able to trigger, in the absence of RUNX1, the down-regulation of endothelial markers and the formation of round cells, a morphologic change characteristic of EHT. Conversely, blood progenitors in Gfi1- and Gfi1b-deficient embryos maintain the expression of endothelial genes. Moreover, those cells are not released from the yolk sac and disseminated into embryonic tissues. Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2011-10-386094DOI Listing
July 2012

Identification and characterization of a novel transcriptional target of RUNX1/AML1 at the onset of hematopoietic development.

Blood 2011 Jul 15;118(3):594-7. Epub 2011 Apr 15.

Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.

Although the critical requirement for the transcription factor RUNX1/AML1 at the onset of hematopoietic development is well established, little is known about its transcriptional targets at this pivotal stage of blood development. Using microarrays, we identified the uncharacterized gene AI467606 as a gene whose expression level is dramatically reduced in the absence of RUNX1. We further demonstrated by chromatin immunoprecipitation and promoter assay a direct regulation of its transcription by RUNX1. Using a bacterial artificial chromosome transgenic approach, we established that AI467606 is expressed during the development of the hematopoietic system in vivo and in vitro and that its expression is detected within the CD41(+) population and marks definitive hematopoietic potential. Similarly, in the adult mouse, all hematopoietic cell lineages, except mature erythrocytes, express AI467606. Taken together, these findings indicate that AI467606 is a novel transcriptional target of RUNX1/AML1 at the onset of hematopoietic development that is extensively expressed within the hematopoietic system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2010-06-294124DOI Listing
July 2011

The sequential expression of CD40 and Icam2 defines progressive steps in the formation of blood precursors from the mesoderm germ layer.

Stem Cells 2010 Jun;28(6):1089-98

Cancer Research UK Stem Cell Hematopoiesis Group, University of Manchester, Manchester, UK.

During embryogenesis, the hematopoietic program is specified from the mesodermal germ layer through the formation of hemangioblast. This precursor gives rise to a hemogenic endothelium that later on matures to generate primitive and definitive hematopoietic precursors. A lack of specific cell surface markers to identify cells with discrete developmental potential is a major hurdle in the quest to further understand the cellular and molecular program governing blood formation. In the present study, we identify CD40 and Icam2, two markers typically associated with the adult immunological compartment, as expressed at the earliest stages of blood specification both in vitro and in vivo. Using in vitro serum-free culture conditions that support the efficient and directed differentiation of embryonic stem cells, we show that the sequential expression of CD40 and Icam2 delineate a transition in the acquisition of the blood potential from hemangioblast to hemogenic endothelium leading to the formation of primitive and definitive hematopoietic progenitors. CD40 is transiently expressed at the onset of blood development and marks first the hemangioblast then the hemogenic endothelium but is no longer expressed on fully committed hematopoietic precursors within the fetal liver. In contrast, Icam2 is first expressed on the hemogenic endothelium and its expression persists on fetal liver hematopoietic progenitors. Taken together, our data identify novel cell surface markers allowing us to further refine our understanding of the events marking progressive hematopoietic commitment from the mesoderm germ layer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/stem.434DOI Listing
June 2010

The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.

Blood 2009 Dec 26;114(26):5279-89. Epub 2009 Oct 26.

Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.

The transcription factor RUNX1/AML1 is a master regulator of hematopoietic development. Its spatiotemporal expression is tightly regulated during embryonic development and is under the control of 2 alternative promoters, distal and proximal. Despite the functional significance of Runx1, the relative and specific activities of these 2 promoters remain largely uncharacterized. To investigate these activities, we introduced 2 reporter genes under the control of the proximal and distal promoters in embryonic stem cell and transgenic mouse lines. Our study reveals that both in vitro and in vivo the proximal Runx1 isoform marks a hemogenic endothelium cell population, whereas the subsequent expression of distal Runx1 defines fully committed definitive hematopoietic progenitors. Interestingly, hematopoietic commitment in distal Runx1 knockout embryos appears normal. Altogether, our data demonstrate that the differential activities of the 2 Runx1 promoters define milestones of hematopoietic development and suggest that the proximal isoform plays a critical role in the generation of hematopoietic cells from hemogenic endothelium. Identification and access to the discrete stages of hematopoietic development defined by the activities of the Runx1 promoters will provide the opportunity to further explore the cellular and molecular mechanisms of hematopoietic development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2009-05-222307DOI Listing
December 2009

Blood cell generation from the hemangioblast.

J Mol Med (Berl) 2010 Feb 25;88(2):167-72. Epub 2009 Oct 25.

Cancer Research UK, Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.

Understanding how blood cells are generated is important from a biological perspective but also has potential implications in the treatment of blood diseases. Such knowledge could potentially lead to defining new conditions to amplify hematopoietic stem cells (HSCs) or could translate into new methods to produce HSCs, or other types of blood cells, from human embryonic stem cells or induced pluripotent stem cells. Additionally, as most key transcription factors regulating early hematopoietic development have also been implicated in various types of leukemia, understanding their function during normal development could result in a better comprehension of their roles during abnormal hematopoiesis in leukemia. In this review, we discuss our current understanding of the molecular and cellular mechanisms of blood development from the earliest hematopoietic precursor, the hemangioblast, a precursor for both endothelial and hematopoietic cell lineages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-009-0554-0DOI Listing
February 2010

Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program.

Blood 2009 Jul 1;114(2):299-309. Epub 2009 Apr 1.

Leeds Institute for Molecular Medicine, University of Leeds, Leeds, United Kingdom.

At the cellular level, development progresses through successive regulatory states, each characterized by their specific gene expression profile. However, the molecular mechanisms regulating first the priming and then maintenance of gene expression within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions and here we have focused on a regulatory circuit playing a central role in myelopoiesis: the transcription factor PU.1, its target gene colony-stimulating-factor 1 receptor (Csf1r), and key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes the establishment of active histone marks and the formation of stable transcription factor complexes at the Pu.1 locus and we show that chromatin remodeling is mediated by the transient binding of RUNX1 to Pu.1 cis-elements. By contrast, chromatin reorganization of Csf1r requires prior expression of PU.1 together with RUNX1 binding. Once the full hematopoietic program is established, stable transcription factor complexes and active chromatin can be maintained without RUNX1. Our experiments therefore demonstrate how individual transcription factors function in a differentiation stage-specific manner to differentially affect the initiation versus maintenance of a developmental program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2008-11-191890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714206PMC
July 2009

In vitro differentiation of mouse embryonic stem cells as a model of early hematopoietic development.

Methods Mol Biol 2009 ;538:317-34

Stem Cell Biology and Research, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.

Embryonic Stem (ES) are pluripotent cells derived from the inner cell mass of blastocysts. ES cells differentiate in vitro into all kind of cells and the development of endothelial and hematopoietic cells from mouse ES cells has been especially established. As such, the in vitro differentiation of ES cells provides a powerful experimental model to study and determine the role of specific genes in the development of the hematopoietic system. Using this approach we have demonstrated the critical function of the transcription factor AML1/Runx1 at the onset of hematopoietic development (Blood 100:458-466, 2002; Blood 103:886-889, 2004). In this chapter, we will describe our protocols and methods for the culture of healthy ES cells, their effective differentiation toward hematopoiesis, and the quantitative analysis of their hematopoietic potential by replating or gene expression analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-59745-418-6_16DOI Listing
May 2009

The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage.

Nature 2009 Feb 28;457(7231):892-5. Epub 2009 Jan 28.

Cancer Research UK Stem Cell Biology Group.

It has been proposed that during embryonic development haematopoietic cells arise from a mesodermal progenitor with both endothelial and haematopoietic potential called the haemangioblast. A conflicting theory instead associates the first haematopoietic cells with a phenotypically differentiated endothelial cell that has haematopoietic potential (that is, a haemogenic endothelium). Support for the haemangioblast concept was initially provided by the identification during mouse embryonic stem cell differentiation of a clonal precursor, the blast colony-forming cell (BL-CFC), which gives rise to blast colonies with both endothelial and haematopoietic components. Although recent studies have now provided evidence for the presence of this bipotential precursor in vivo, the precise mechanism for generation of haematopoietic cells from the haemangioblast still remains completely unknown. Here we demonstrate that the haemangioblast generates haematopoietic cells through the formation of a haemogenic endothelium intermediate, providing the first direct link between these two precursor populations. The cell population containing the haemogenic endothelium is transiently generated during BL-CFC development. This cell population is also present in gastrulating mouse embryos and generates haematopoietic cells on further culture. At the molecular level, we demonstrate that the transcription factor Tal1 (also known as Scl; ref. 10) is indispensable for the establishment of this haemogenic endothelium population whereas the core binding factor Runx1 (also known as AML1; ref. 11) is critical for generation of definitive haematopoietic cells from haemogenic endothelium. Together our results merge the two a priori conflicting theories on the origin of haematopoietic development into a single linear developmental process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature07679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661201PMC
February 2009

Extrathymic hemopoietic progenitors committed to T cell differentiation in the adult mouse.

J Immunol 2005 Feb;174(4):1980-8

Institut National de la Sant é et de la Recherche Médicale Unit é 591, Institut Necker, Faculté de Médecine René Descartes Paris V, Paris, France.

The role of the thymus in T cell commitment of hemopoietic precursor is yet controversial. We previously identified a major T cell progenitor activity in precursor cells isolated from bone marrow-derived spleen colonies. In this study, we characterize the properties of these pre-T cells. We demonstrate that they have unique phenotype and can be generated in a total absence of any thymic influence. Indeed, even when studied at the single-cell level, extrathymic T cell-committed precursors express T cell-specific genes. Moreover, these cells are not committed to a particular T cell differentiation pathway because they can generate both extrathymic CD8alphaalpha+ intraepithelial lymphocytes and thymus-derived conventional thymocytes. We also compared these pre-T cells with fully T cell-committed thymic progenitors. When tested in vitro or by direct intrathymic transfer, these cells have a low clonogenic activity. However, after i.v. transfer, thymus repopulation is efficient and these precursors generate very high numbers of peripheral T cells. These results suggest the existence of extra steps of pre-T cell maturation that improve thymus reconstitution capacity and that can be delivered even after full T cell commitment. Consequently, our studies identify a source of extrathymic progenitors that will be helpful in defining the role of the thymus in the earliest steps of T cell differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.174.4.1980DOI Listing
February 2005

Major T cell progenitor activity in bone marrow-derived spleen colonies.

J Exp Med 2002 Apr;195(7):919-29

INSERM U345, Institut Necker. CNRS UMR 8603, Hôpital Necker. IFR 94 (Institut Fédératif de Recherche Necker-Enfants-Malades), 75730 Paris Cedex 15, France.

Common lymphoid progenitors (CLP) are generated in adult bone marrow (BM), but the intermediate steps leading to T cell commitment are unknown, and so is the site at which this commitment occurs. Here, we show that colonies arising in the spleen 12 days after BM injection harbor T cell precursors that are undetectable in BM. These precursors did not generate myeloid cells in vivo but repopulated the thymus and the peripheral T cell compartment much faster than did CLP. Two lineage negative (Lin(-)) subpopulations were distinguished, namely CD44(+) Thy1(-) cells still capable of natural killer generation and transient low-level B cell generation, and T cell-restricted CD44(-) Thy1(+) cells. At a molecular level, frequency of CD3epsilon and preTalpha mRNA was very different in each subset. Furthermore, only the CD44(-) Thy1(+) subset have initiated rearrangements in the T cell receptor beta locus. Thus, this study identifies extramedullary T cell progenitors and will allow easy approach to T cell commitment studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193723PMC
http://dx.doi.org/10.1084/jem.20011475DOI Listing
April 2002