Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 896-903 ◽  
Author(s):  
Hiroshi Sakamoto ◽  
Guoyou Dai ◽  
Kaori Tsujino ◽  
Kazuaki Hashimoto ◽  
Xin Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
B Lymphocyte ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Cell Development ◽  
Hematopoietic Cell ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Cell Lineage

Abstract The definitive hematopoietic cell lineages have been proposed to originate from hemogenic endothelial cells during mouse embryogenesis. c-Myb is a transcription factor that is essential for the development of definitive hematopoiesis. To investigate the functional role of c-Myb in hematopoietic cell development from endothelial cells, we introduced a c-myb transgene expressed under the control of a tetracycline-regulated promoter into the c-myb–/– embryonic stem (ES) cell line, with the aim of inducing c-Myb expression at any stage and at any level. Induction of c-Myb expression after replating c-myb–/– endothelial cells rescued the generation and proliferation of definitive hematopoietic progenitor cells, suggesting that c-Myb expression in developing endothelial cells is not a prerequisite for their hematogenic potential. Overexpression of c-Myb, however, prevented the terminal differentiation of erythrocytes and megakaryocytes and completely abolished B-lymphocyte development. Our results indicate that c-Myb is a major factor that controls differentiation as well as proliferation of hematopoietic progenitor cells derived from hemogenic endothelial cells, and that appropriate levels of c-Myb protein are strictly defined at distinct differentiation steps of each hematopoietic cell lineage.

Expression of 4-Integrin Defines the Earliest Precursor of Hematopoietic Cell Lineage Diverged From Endothelial Cells

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1168-1177 ◽  
Author(s):  
Minetaro Ogawa ◽  
Masami Kizumoto ◽  
Satomi Nishikawa ◽  
Tetsuhiro Fujimoto ◽  
Hiroaki Kodama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Cell Population ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Hematopoietic Cell ◽  
Hematopoietic Stem ◽  
Hematopoietic Cell Lineage ◽  
E Cadherin

Abstract Embryonic stem cells can differentiate in vitro into hematopoietic cells through two intermediate stages; the first being FLK1+ E-cadherin− proximal lateral mesoderm and the second being CD45− VE-cadherin+endothelial cells. To further dissect the CD45−VE-cadherin+ cells, we have examined distribution of 4-integrin on this cell population, because 4-integrin is the molecule expressed on hematopoietic stem cells. During culture of FLK1+ E-cadherin− cells, CD45− VE-cadherin+4-integrin− cells differentiate first, followed by 4-integrin+ cells appearing in both CD45− VE-cadherin+ and CD45−VE-cadherin− cell populations. In the CD45−VE-cadherin+ cell population, 4-integrin+ subset but not 4-integrin− subset had the potential to differentiate to hematopoietic lineage cells, whereas endothelial cell progenitors were present in both subsets. The CD45−VE-cadherin− 4-integrin+ cells also showed hematopoietic potential. Reverse transcription-polymerase chain reaction analyses showed that differential expression of the Gata2 and Myb genes correlated with the potential of the 4-integrin+ cells to give rise to hematopoietic cell differentiation. Hematopoietic CD45−VE-cadherin+ 4-integrin+ cells were also present in the yolk sac and embryonic body proper of 9.5 day postcoitum mouse embryos. Our results suggest that the expression of 4-integrin is a marker of the earliest precursor of hematopoietic cell lineage that was diverged from endothelial progenitors.

Lineage Instructive Function of C/EBPα in Multipotent Hematopoietic Progenitor Cells Revealed in a Novel Cebpa-Cre Knock-in Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2458-2458
Author(s):  
Albert Wolfler ◽  
Astrid A Danen-van Oorschot ◽  
Jurgen Haanstra ◽  
Marijke Valkhof ◽  
Paulette van Strien ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Cell Development ◽  
Hematopoietic Cell ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Multipotent Progenitors ◽  
Reported Data

Abstract Transcription factors control the lineage specification and differentiation of hematopoietic progenitor cells. They are expressed in a cell type-restricted pattern and activate lineage specific genetic programs. Recent studies have demonstrated that expression of GATA-1 or PU.1 in multipotent lin−Sca-1+c-Kit+ (LSK) cells specifies them to develop into myeloerythroid progenitors or lymphomyeloid progenitors, respectively. In contrast, C/EBPα, a transcription factor indispensable for the production of granulocytes and macrophages, is thought to predominantly act at a later stage of hematopoietic commitment, by governing the transition from common myeloid progenitors (CMPs) into granulocytic/monocytic progenitors (GMPs). To study whether C/EBPα may already exert a lineage instructive function at an earlier stage of hematopoietic cell development, i.e., at the level of multipotent LSK cells, we generated a knock-in mouse model expressing Cre recombinase under the regulation of the cebpa promoter and crossed C/EBPαcre/+ mice with R26 YFP reporter mice. This model faithfully demonstrates high levels of C/EBPα expression in myeloid cells and enabled us to trace cebpa-driven Cre/YFP expression in single LSK cells and their progeny by flow cytometry and colony cultures. On average cebpa-driven YFP expression was found in 17% (range 10–25%) of the total LSK fraction (n=12 mice). Within the CD150+CD48− CD34− subset of LSK cells, which contains the most primitive hematopoietic stem cells (HSC), 3–8% of the cells expressed YFP, indicating that cebpa is lowly expressed in bona fide HSC. This low level of expression appears insufficient for lineage determination, since the same levels of YFP expression (1–10%) were found in peripheral T and B cells. Within the CD34+ fraction of LSK cells, a population enriched for multipotent progenitors, 19% (range 14%–28%) of the cells expressed YFP. Identical distributions of YFP+ cells among the different LSK subsets were found in fetal livers of day 14.5 embryos, suggesting a comparable regulation of cebpa expression in fetal and adult cells. Similar to the reported data for GATA-1 and PU.1, cebpa-expressing LSK cells were predominantly found in the Sca-1low fraction. When cultured in a multilineage cytokine cocktail, YFP+ LSK cells gave predominantly rise to GM colonies (73% of all colonies; range 65–85%), whereas YFP− cells formed multiple types of colonies including mixed, megakaryocytic and erythroid colonies. The predominant outgrowth of YFP+ LSK cells to GM lineages was further supported in GM-CSF-supplemented colony assays, which gave rise to cloning efficiencies of 26% for YFP+ and 4% for YFP− LSK cells, respectively. In conclusion, our results show that C/EBPα starts to exert its instructive function towards GM cell development already within the LSK population, at the level of the multipotent progenitors. This has important ramifications for our understanding of the role of C/EBPα in early hematopoietic cell fate decisions.

Expression of 4-Integrin Defines the Earliest Precursor of Hematopoietic Cell Lineage Diverged From Endothelial Cells

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1168-1177 ◽  
Author(s):  
Minetaro Ogawa ◽  
Masami Kizumoto ◽  
Satomi Nishikawa ◽  
Tetsuhiro Fujimoto ◽  
Hiroaki Kodama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Cell Population ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Hematopoietic Cell ◽  
Hematopoietic Stem ◽  
Hematopoietic Cell Lineage ◽  
E Cadherin

Embryonic stem cells can differentiate in vitro into hematopoietic cells through two intermediate stages; the first being FLK1+ E-cadherin− proximal lateral mesoderm and the second being CD45− VE-cadherin+endothelial cells. To further dissect the CD45−VE-cadherin+ cells, we have examined distribution of 4-integrin on this cell population, because 4-integrin is the molecule expressed on hematopoietic stem cells. During culture of FLK1+ E-cadherin− cells, CD45− VE-cadherin+4-integrin− cells differentiate first, followed by 4-integrin+ cells appearing in both CD45− VE-cadherin+ and CD45−VE-cadherin− cell populations. In the CD45−VE-cadherin+ cell population, 4-integrin+ subset but not 4-integrin− subset had the potential to differentiate to hematopoietic lineage cells, whereas endothelial cell progenitors were present in both subsets. The CD45−VE-cadherin− 4-integrin+ cells also showed hematopoietic potential. Reverse transcription-polymerase chain reaction analyses showed that differential expression of the Gata2 and Myb genes correlated with the potential of the 4-integrin+ cells to give rise to hematopoietic cell differentiation. Hematopoietic CD45−VE-cadherin+ 4-integrin+ cells were also present in the yolk sac and embryonic body proper of 9.5 day postcoitum mouse embryos. Our results suggest that the expression of 4-integrin is a marker of the earliest precursor of hematopoietic cell lineage that was diverged from endothelial progenitors.

scholarly journals Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood–derived hematopoietic progenitor cells

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2730-2737 ◽  
Author(s):  
Colin H. Martin ◽  
Petter S. Woll ◽  
Zhenya Ni ◽  
Juan Carlos Zúñiga-Pflücker ◽  
Dan S. Kaufman
Keyword(s):  
Stem Cell ◽  
B Cells ◽  
Progenitor Cells ◽  
Embryonic Stem ◽  
Cell Development ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Developmental Potential ◽  
Cd34 Cells

Abstract Hematopoietic progenitor cells derived from human embryonic stem cells (hESCs) develop into diverse mature hematopoietic lineages, including lymphocytes. Whereas functional natural killer (NK) cells can be efficiently generated in vitro from hESC-derived CD34+ cells, studies of T- and B-cell development from hESCs have been much more limited. Here, we demonstrate that despite expressing functional Notch-1, CD34+ cells from hESCs did not derive T cells when cocultured with OP9 cells expressing Delta-like 1, or in fetal thymus organ culture. hESC-derived CD34+ cells also did not produce B cells in vitro. In contrast, CD34+ cells isolated from UCB routinely generated T and B cells when cultured in the same conditions. Notably, both undifferentiated hESCs, and sorted hESC-derived populations with hematopoietic developmental potential exhibited constitutive expression of ID family genes and of transcriptional targets of stem cell factor–induced signaling. These pathways both inhibit T-cell development and promote NK-cell development. Together, these results demonstrate fundamental differences between hESC-derived hematopoietic progenitors and analogous primary human cells. Therefore, hESCs can be more readily supported to differentiate into certain cell types than others, findings that have important implications for derivation of defined lineage-committed populations from hESCs.

scholarly journals Hematopoietic Cell Transplantation for Sickle Cell Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Lakshmanan Krishnamurti
Keyword(s):  
Sickle Cell Disease ◽  
Progenitor Cells ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Hematopoietic Progenitor Cells ◽  
Cell Disease ◽  
Hematopoietic Progenitor ◽  
Erythrocyte Deformation

Sickle cell disease (SCD) is a severe autosomal recessively inherited disorder of the red blood cell characterized by erythrocyte deformation caused by the polymerization of the abnormal hemoglobin, which leads to erythrocyte deformation and triggers downstream pathological changes. These include abnormal rheology, vaso-occlusion, ischemic tissue damage, and hemolysis-associated endothelial dysfunction. These acute and chronic physiologic disturbances contribute to morbidity, organ dysfunction, and diminished survival. Hematopoietic cell transplantation (HCT) from HLA-matched or unrelated donors or haploidentical related donors or genetically modified autologous hematopoietic progenitor cells is performed with the intent of cure or long-term amelioration of disease manifestations. Excellent outcomes have been observed following HLA-identical matched related donor HCT. The majority of SCD patients do not have an available HLA-identical sibling donor. Increasingly, however, they have the option of undergoing HCT from unrelated HLA matched or related haploidentical donors. The preliminary results of transplantation of autologous hematopoietic progenitor cells genetically modified by adding a non-sickling gene or by genomic editing to increase expression of fetal hemoglobin are encouraging. These approaches are being evaluated in early-phase clinical trials. In performing HCT in patients with SCD, careful consideration must be given to patient and donor selection, conditioning and graft-vs.-host disease regimen, and pre-HCT evaluation and management during and after HCT. Sociodemographic factors may also impact awareness of and access to HCT. Further, there is a substantial decisional dilemma in HCT with complex tradeoffs between the possibility of amelioration of disease manifestations and early or late complications of HCT. The performance of HCT for SCD requires careful multidisciplinary collaboration and shared decision making between the physician and informed patients and caregivers.

scholarly journals EP-1609: Circulating hematopoietic progenitor cells and endothelial cells in prostate cancer under SBRT

2018 ◽  
Vol 127 ◽  
pp. S866
Author(s):  
C. Cigarral García ◽  
L.I. Sánchez-Abarca Bernal ◽  
C. Rodríguez Serrano ◽  
V. Macías Hernández ◽  
M.P. García Rodríguez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor
Sign in / Sign up

Export Citation Format

Share Document