scholarly journals Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells

Lab on a Chip ◽  
2009 ◽  
Vol 9 (18) ◽  
pp. 2659 ◽  
Author(s):  
Shannon L. Faley ◽  
Mhairi Copland ◽  
Donald Wlodkowic ◽  
Walter Kolch ◽  
Kevin T. Seale ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Hematopoietic Stem ◽  
Cell Arrays

Single-cell analyses show TGF-b1 reduces self-renewal and myeloid differentiation potentials in hematopoietic stem cells

2017 ◽  
Vol 53 ◽  
pp. S109-S110
Author(s):  
Xiaofang Wang ◽  
Fang Dong ◽  
Sen Zhang ◽  
Wanzhu Yang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Myeloid Differentiation ◽  
Self Renewal ◽  
Hematopoietic Stem

scholarly journals Reconstructing Boolean network ensembles from single-cell data for unraveling dynamics in the aging of human hematopoietic stem cells

2021 ◽  
Vol 19 ◽  
pp. 5321-5332
Author(s):  
Julian D. Schwab ◽  
Nensi Ikonomi ◽  
Silke D. Werle ◽  
Felix M. Weidner ◽  
Hartmut Geiger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Boolean Network ◽  
Hematopoietic Stem ◽  
Network Ensembles ◽  
Cell Data

scholarly journals Signaling Profiling at the Single-Cell Level Identifies a Distinct Signaling Signature in Murine Hematopoietic Stem Cells

Stem Cells ◽  
2012 ◽  
Vol 30 (7) ◽  
pp. 1447-1454 ◽  
Author(s):  
Juan Du ◽  
Jinyong Wang ◽  
Guangyao Kong ◽  
Jing Jiang ◽  
Jingfang Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Single Cell Level ◽  
Cell Level ◽  
Hematopoietic Stem

On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup

2012 ◽  
Vol 40 (2) ◽  
pp. 119-130.e9 ◽  
Author(s):  
Nico Scherf ◽  
Katja Franke ◽  
Ingmar Glauche ◽  
Ina Kurth ◽  
Martin Bornhäuser ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Cell Tracking ◽  
Hematopoietic Stem

Evidence for a Novel Blood Lineage Commitment Pathway from Lympho-Myeloid Hematopoietic Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 802-802 ◽  
Author(s):  
Sten Eirik W. Jacobsen ◽  
Robert Mansson ◽  
Anne Hultquist ◽  
Mikael Sigvardsson ◽  
Natalija Buza-Vidas ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Lineage Commitment ◽  
Mouse Bone Marrow ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Stage Of Development ◽  
Number Of Genes

Abstract We recently identified a novel Lin−Sca-1+c-kithiCD34+Flt3hi (LSKCD34+Flt3hi) lymphoid-primed multipotent progenitor (LMPP) in adult mouse bone marrow which, although possessing a combined lymphoid (B and T cell) and myeloid (granulocyte-monocyte; GM) differentiation potential, have little or no ability to adopt erythroid (E) and megakaryocyte (MK) lineage fates (Adolfsson et al, Cell121:295, 2005). The identification of this lineage restricted lymphomyeloid progenitor implicates the existence of alternative roadmaps for lineage commitment of pluripotent hematopoietic stem cells (HSCs), distinct from the classical model suggesting that the first HSC commitment step results in a strict separation into common lymphoid and myeloid progenitors. Herein we provide further, genetic evidence for such a model. Affymetrix global gene profiling, quantitative PCR, and multiplex single cell PCR analysis of LSKCD34−Flt3− long-term (LT)-HSCs, LSKCD34+Flt3− short-term (ST)-HSCs and LSKCD34+Flt3hi LMPPs, demonstrate that LMPPs in contrast to LT-HSCs and ST-HSCs down-regulate or turn off a number of genes critically involved in MkE lineage development, including GATA-1 and the receptors for erythropoietin and thrombopoietin. In contrast, a number of genes specific for early lymphoid development, including Rag-1, sterile Ig and IL-7 receptor are upregulated in LMPPs but absent in LT-HSCs and ST-HSCs. Importantly, within the LMPP, these lymphoid genes are typically co-expressed with a number of GM associated genes such as G-CSF receptor and MPO, but virtually never co-expressed with MkE associated genes. Investigating fetal liver day 14.5 we also provide evidence for existence of the LSKCD34+Flt3hi LMPPs at this early stage of development, and using a single cell clonal assay promoting combined B, T and myeloid lineage development, we demonstrate that a large fraction of fetal LMPPs lacking MkE potential possess a combined GM, B and T cell potential. Thus, evaluation at the single cell level of combined lineage potentials and multilineage gene expression provide compelling evidence for lymphoid-priming within the HSC compartment being preceeded by a loss of MkE potential, but occurring prior to loss of GM potential.

scholarly journals Single-cell transcriptome analysis of embryonic and adult endothelial cells allows to rank the hemogenic potential of post-natal endothelium

2021 ◽  
Author(s):  
Artem Adamov ◽  
Yasmin Natalia Serina Sechanecia ◽  
Christophe Lancrin
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Rational Design ◽  
Continuous Production ◽  
Cellular Reprogramming ◽  
Hematopoietic Stem ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Hematopoietic stem cells are crucial for the continuous production of blood cells during life. The transplantation of these cells is one of the most common treatments to cure patient suffering of blood diseases. However, the lack of suitable donors is a major limitation. One option to get hematopoietic stem cells matching perfectly a patient is cellular reprogramming. Hematopoietic stem cells emerge from endothelial cells in blood vessels during embryogenesis through the endothelial to hematopoietic transition. Here, we used single-cell transcriptomics analysis to compare embryonic and post-natal endothelial cells to investigate the potential of adult vasculature to be reprogrammed in hematopoietic stem cells. Although transcriptional similarities have been found between embryonic and adult endothelial cells, we found some key differences in term of transcription factors expression. There is a deficit of expression of Runx1, Tal1, Lyl1 and Cbfb in adult endothelial cells compared to their embryonic counterparts. Using a combination of gene expression profiling and gene regulatory network analysis, we found that endothelial cells from the pancreas, brain, kidney and liver appear to be the most suitable targets for cellular reprogramming into hematopoietic stem cells. Overall, our work provides an important resource for the rational design of a reprogramming strategy for the generation of hematopoietic stem cells.

scholarly journals Transcriptional and Functional Description of Stem Cell Heterogeneity in Native and Transplantation Hematopoiesis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3844-3844
Author(s):  
Alejo E Rodriguez-Fraticelli ◽  
Caleb Weinreb ◽  
Allon Moshe Klein ◽  
Fernando Camargo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Significant Proportion ◽  
Cell Heterogeneity ◽  
Hematopoietic Stem

Abstract The hematopoietic system follows a hierarchical organization, with multipotent long-term repopulating hematopoietic stem cells (LT-HSCs) occupying the top tier. This paradigm, developed mostly through cell transplantation assays, has recently been contested by a series of studies performed under native conditions, without transplantation. Application of systems-level single cell methods in this setting has revealed a heterogeneity of cell states within progenitors and stem cells, prompting a reevaluation of the theories of hematopoietic lineage fate decisions. We have previously described that hematopoietic stem cell fates are clonally heterogeneous under steady state and uncovered that a fraction of LT-HSCs contributes to a significant proportion of the megakaryocytic cell lineage under steady state, while rarely generating other types of progeny in unperturbed conditions. To elucidate the molecular underpinnings of this functional lineage-output heterogeneity, we developed a technique to barcode hematopoietic cells at the RNA level in order to simultaneously capture the lineage relationships and transcriptional states of HSCs. Using a droplet-based massive single cell RNAseq platform, we analyzed thousands of engrafted hematopoietic stem cells together with a sufficiently significant representation of downstream progenitor cells to measure HSC output. Inspection of the resulting "stem cell state-fate maps" revealed a variety of stem cell behaviors, including single cell quiescence, asymmetric and symmetric divisions, and clonal expansion. We also connected these behaviors with some of the previously observed heterogeneity in stem cell outcomes, including lineage bias, lineage output and clonal competition. Importantly, clustering of expression profiles revealed significant differences in the transcriptional programs related with some of these behaviors, which illuminate the molecular machineries that operate at the stem cell level to define this heterogeneity. Thus, our work has identified potential novel mediators for stem cell heterogeneity, which we are functionally analyzing in further detail to understand their molecular mechanisms. Disclosures No relevant conflicts of interest to declare.

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