3063 – DISTINCT POPULATIONS OF MULTIPOTENT PROGENITORS AND HEMATOPOIETIC STEM CELLS EMERGE FROM HEMOGENIC ENDOTHELIUM IN THE MURINE EMBRYO

2020 ◽  
Vol 88 ◽  
pp. S57-S58
Author(s):  
Tessa Dignum ◽  
Barbara Varnum-Finney ◽  
Sanjay Srivatsan ◽  
Stacey Dozono ◽  
Olivia Waltner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
Murine Embryo

scholarly journals Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo

Cell Reports ◽  
2021 ◽  
Vol 36 (11) ◽  
pp. 109675
Author(s):  
Tessa Dignum ◽  
Barbara Varnum-Finney ◽  
Sanjay R. Srivatsan ◽  
Stacey Dozono ◽  
Olivia Waltner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Mouse Embryo ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors

scholarly journals Hematopoietic Stem Cells Are Endowed with Erythroid Signature in Beta-Thalassemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-31
Author(s):  
Maria Rosa Lidonnici ◽  
Giulia Chianella ◽  
Francesca Tiboni ◽  
Matteo Barcella ◽  
Ivan Merelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Gene Set Enrichment Analysis ◽  
Lineage Commitment ◽  
Erythroid Cell ◽  
Beta Thalassemia ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors

Background Beta-thalassemia (Bthal) is a genetic disorder due to mutations in the ß-globin gene, leading to a reduced or absent production of HbA, which interferes with erythroid cell maturation and limits normal red cell production. Patients are affected by severe anemia, hepatosplenomegaly, and skeletal abnormalities due to rapid expansion of the erythroid compartment in bone marrow (BM) caused by ineffective erythropoiesis. In a classical view of hematopoiesis, the blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. In human, novel purification strategies based on differential expression of CD49f and CD90 enrich for long-term (49f+) and short-term (49f−) repopulating hematopoietic stem cells (HSCs), with distinct cell cycle properties, but similar myeloid (My) and lymphoid (Ly) potential. In this view, it has been proposed that erythroid (Ery) and megakaryocytic (Mk) fates branch off directly from CD90-/49f− multipotent progenitors (MPPs). Recently, a new study suggested that separation between multipotent (Ery/My/Ly) long-term repopulating cells (Subset1, defined as CLEC9AhighCD34low) and cells with only My/Ly and no Ery potential (Subset2, defined as CLEC9AlowCD34high)occurs within the phenotypic HSC/MPP and CD49f+ HSCs compartment. Aims A general perturbed and stress condition is present in the thalassemic BM microenvironment. Since its impact on the hematopoietic cell subpopulations is mostly unknown, we will investigate which model of hematopoiesis/erythropoiesis occurs in Bthal. Moreover, since Beta-Thalassemia is an erythropoietic disorder, it could be considered as a disease model to study the 'erythroid branching' in the hematopoietic hierarchy. Methods We defined by immunophenotype and functional analysis the lineage commitment of most primitive HSC/MPP cells in patients affected by this pathology compared to healthy donors (HDs). Furthermore, in order to delineate the transcriptional networks governing hematopoiesis in Beta-thalassemia, RNAseq analysis was performed on sorted hematopoietic subpopulations from BM of Bthal patients and HDs. By droplet digital PCR on RNA purified from mesenchymal stromal cells of Bthal patients, we evaluated the expression levels of some niche factors involved in the regulation of hematopoiesis and erythropoiesis. Moreover, the protein levels in the BM plasma were analyzed by performing ELISA. Results Differences in the primitive compartment were observed with an increased proportion of multipotent progenitors in Bthal patients compared to HDs. The Subset1 compartment is actually endowed with an enhanced Ery potential. Focusing on progenitors (CD34+ CD38+) and using a new sorting scheme that efficiently resolved My, Ery, and Mk lineage fates, we quantified the new My (CD71-BAH1-/+) and Ery (CD71+ BAH1-/+) subsets and found a reduction of Ery subset in Bthal samples. We can hypothesize that the erythroid-enriched subsets are more prone to differentiate quickly due to the higher sensitivity to Epo stimuli or other bone marrow niche signals. Gene set enrichment analysis, perfomed on RNAseq data, showed that Bthal HSC/MPP presented negative enrichment of several pathways related to stemness and quiescence. Cellular processes involved in erythropoiesis were found altered in Bthal HSC. Moreover, some master erythroid transcription factors involved were overrepresented in Bthal across the hematopoietic cascade. We identified the niche factors which affect molecular pathways and the lineage commitment of Bthal HSCs. Summary/Conclusions Overall, these data indicate that Bthal HSCs are more cycling cells which egress from the quiescent state probably towards an erythroid differentiation, probably in response to a chronic BM stimulation. On the other hand,some evidences support our hypothesis of an 'erythroid branching' already present in the HSC pool, exacerbated by the pathophysiology of the disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gene Coexpression Analysis in Single Cells Indicates Lymphomyeloid Copriming in Short-Term Hematopoietic Stem Cells and Multipotent Progenitors

2010 ◽  
Vol 184 (9) ◽  
pp. 4907-4917 ◽  
Author(s):  
Laetitia Gautreau ◽  
Amine Boudil ◽  
Valérie Pasqualetto ◽  
Lamia Skhiri ◽  
Laure Grandin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cells ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Coexpression Analysis ◽  
Gene Coexpression ◽  
Multipotent Progenitors

scholarly journals The CD11a and EPCR marker combination simplifies and improves the purification of mouse hematopoietic stem cells

2017 ◽  
Author(s):  
Alborz Karimzadeh ◽  
Vanessa Scarfone ◽  
Connie Chao ◽  
Karin Grathwohl ◽  
John W. Fathman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Gold Standard ◽  
Cell Types ◽  
The Self ◽  
Mouse Bone Marrow ◽  
Surface Markers ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
Marker Combination

AbstractHematopoietic 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 it 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, 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.Significance StatementThe study of hematopoietic stem cells (HSCs) and their purification for transplantation requires a panel of surface markers that can be used to distinguish HSCs from other cell types. The number of markers necessary to identify HSCs continues to grow, making it increasingly difficult to identify HSCs by flow cytometry. In this study, we identified a combination of two surface markers, CD11a and EPCR, to enrich for HSCs in the mouse bone marrow without the need for additional markers. This simplified panel could aid HSC research by reducing the number of markers necessary to identify and isolate HSCs.

Identification of Thymus Settling Progenitors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2677-2677
Author(s):  
Benjamin A. Schwarz ◽  
Avinash Bhandoola
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
Hematopoietic Stem Cells ◽  
Adult Life ◽  
Hematopoietic Stem ◽  
Adult Mice ◽  
Multipotent Progenitors ◽  
Pass Through ◽  
Adult Thymus

Abstract T cells develop in the thymus, but are ultimately derived from hematopoietic stem cells (HSCs) that reside in the bone marrow. In order to produce T cells throughout adult life, the thymus must be periodically seeded by bone marrow progenitors via the blood. The identity of progenitors that seed the adult thymus is unknown. To determine which bone marrow progenitors that have access to they thymus, we analyzed the blood of adult mice (Schwarz & Bhandoola, Nature Immunology 2004). We found that the only progenitors in blood with T lineage potential were lineage negative cells with high expression of Sca-1 and c-Kit (LSK). Such LSK cells in blood were potent T lineage progenitors, with the capacity to expand over a million fold in the thymus. Like the corresponding population in the bone marrow, the blood LSK population was heterogeneous, containing HSCs and downstream multipotent progenitors (MPPs) including RAG-expressing early lymphoid progenitors (ELPs) and CD62L+ cells. In order to determine which of these LSK subsets can settle in the thymus, we developed a quantitative assay for thymic seeding in normal adult mice. We find that the fraction of LSK cells that settle in the thymus from the blood is extremely small. Of the estimated 3,000 to 4,000 LSK cells that pass through the thymic circulation each day, less than 10 cells are able to settle in the thymus. Our data suggest that any decrease in thymic seeding, as may occur in aging, would lead to a decrease in total thymic output.

scholarly journals Murine Hematopoietic Stem Cells and Multipotent Progenitors Express Truncated Intracellular Form of c-kit Receptor

2008 ◽  
Vol 17 (2) ◽  
pp. 343-354 ◽  
Author(s):  
Jennifer Zayas ◽  
Danislav S. Spassov ◽  
Ronald G. Nachtman ◽  
Roland Jurecic
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Intracellular Form ◽  
Multipotent Progenitors ◽  
Kit Receptor

scholarly journals C/EBPα Is Required for Long-Term Self-Renewal and Lineage Priming of Hematopoietic Stem Cells and for the Maintenance of Epigenetic Configurations in Multipotent Progenitors

PLoS Genetics ◽  
2014 ◽  
Vol 10 (1) ◽  
pp. e1004079 ◽  
Author(s):  
Marie S. Hasemann ◽  
Felicia K. B. Lauridsen ◽  
Johannes Waage ◽  
Janus S. Jakobsen ◽  
Anne-Katrine Frank ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
Lineage Priming

scholarly journals The embryonic origins of hematopoietic stem cells: a tale of hemangioblast and hemogenic endothelium

Apmis ◽  
2005 ◽  
Vol 113 (11-12) ◽  
pp. 790-803 ◽  
Author(s):  
KARINE BOLLEROT ◽  
CLAIRE POUGET ◽  
THIERRY JAFFREDO
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem
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