scholarly journals FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4806-4814 ◽  
Author(s):  
Fei Liu ◽  
Jae Y. Lee ◽  
Huijun Wei ◽  
Osamu Tanabe ◽  
James D. Engel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Cells ◽  
Cellular Functions ◽  
Interacting Protein ◽  
Hematopoietic Stem ◽  
Conditional Deletion ◽  
Perinatal Lethality ◽  
Fetal Hematopoiesis ◽  
And Function

Abstract Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs.

scholarly journals Expression and function of adhesion molecules on human hematopoietic stem cells: CD34+ LFA-1- cells are more primitive than CD34+ LFA-1+ cells

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Y Gunji ◽  
M Nakamura ◽  
T Hagiwara ◽  
K Hayakawa ◽  
H Matsushita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Leukocyte Function ◽  
Colony Forming Capacity ◽  
And Function ◽  
Cell Phenotypes

Advances in fluorescence-activated cell sorter technology have brought about multicolor analysis of cell phenotypes. To clarify the phenotypes of human hematopoietic stem cells (HSCs), we initially prepared novel antibodies against CD34 and labeled one of them (4A1) with allophycocyanin (APC). With this, we analyzed the phenotypes of CD34+ HSCs and showed that primitive HSCs or CD34+CD33- cells expressed adhesion molecules such as CD43, CD44, CD11a, CD11c, CD18, and leukocyte adhesion molecule (LAM-1). The more primitive hematopoietic cells or CD34+CD38- cells also expressed CD11a and CD18 with an incidence of 20% to 30%. To clarify the role of adhesion molecules in HSCs, we examined the colony forming capacity after long-term culture with allogeneic irradiated stromal layers. Among CD34+CD33- cells, CD18+ cells gave rise to colony-forming cells (CFCs) on stromal layers, but reached a maximum at week 2, after which the number of generated CFCs decreased. On the other hand, CD18- cells generated less CFCs than CD18+ cells at 2 to 3 weeks, but increased after 4 weeks of culture. When CD18 or CD11a antibody was added to a coculture system of CD34+CD33- cells with stromal layers, the number of generated CFCs decreased significantly compared with the no antibody control. Leukocyte function-associated antigen-1 (LFA-1) (CD11a/CD18) was expressed on some populations of hematopoietic cells and contributed to the proliferation by interacting with stromal cells. However, more primitive cells capable of reconstituting hematopoiesis did not express LFA-1. These data provide a rationale for the administration of anti- LFA-1 antibody after bone marrow transplantation for reducing the graft failure.

scholarly journals Expression and function of adhesion molecules on human hematopoietic stem cells: CD34+ LFA-1- cells are more primitive than CD34+ LFA-1+ cells

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Y Gunji ◽  
M Nakamura ◽  
T Hagiwara ◽  
K Hayakawa ◽  
H Matsushita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Leukocyte Function ◽  
Colony Forming Capacity ◽  
And Function ◽  
Cell Phenotypes

Abstract Advances in fluorescence-activated cell sorter technology have brought about multicolor analysis of cell phenotypes. To clarify the phenotypes of human hematopoietic stem cells (HSCs), we initially prepared novel antibodies against CD34 and labeled one of them (4A1) with allophycocyanin (APC). With this, we analyzed the phenotypes of CD34+ HSCs and showed that primitive HSCs or CD34+CD33- cells expressed adhesion molecules such as CD43, CD44, CD11a, CD11c, CD18, and leukocyte adhesion molecule (LAM-1). The more primitive hematopoietic cells or CD34+CD38- cells also expressed CD11a and CD18 with an incidence of 20% to 30%. To clarify the role of adhesion molecules in HSCs, we examined the colony forming capacity after long-term culture with allogeneic irradiated stromal layers. Among CD34+CD33- cells, CD18+ cells gave rise to colony-forming cells (CFCs) on stromal layers, but reached a maximum at week 2, after which the number of generated CFCs decreased. On the other hand, CD18- cells generated less CFCs than CD18+ cells at 2 to 3 weeks, but increased after 4 weeks of culture. When CD18 or CD11a antibody was added to a coculture system of CD34+CD33- cells with stromal layers, the number of generated CFCs decreased significantly compared with the no antibody control. Leukocyte function-associated antigen-1 (LFA-1) (CD11a/CD18) was expressed on some populations of hematopoietic cells and contributed to the proliferation by interacting with stromal cells. However, more primitive cells capable of reconstituting hematopoiesis did not express LFA-1. These data provide a rationale for the administration of anti- LFA-1 antibody after bone marrow transplantation for reducing the graft failure.

Optimization of cytapheresis products' storage for CD34+ hematopoietic stem cells viability and function maintenance

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S78
Author(s):  
N. Lombion ◽  
C. Gouat ◽  
D. Tramalloni ◽  
V. Lapierre ◽  
B.S. Marteyn
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
And Function

scholarly journals Thrombopoietin Induces HOXA9 Nuclear Transport in Immature Hematopoietic Cells: Potential Mechanism by Which the Hormone Favorably Affects Hematopoietic Stem Cells

2004 ◽  
Vol 24 (15) ◽  
pp. 6751-6762 ◽  
Author(s):  
Keita Kirito ◽  
Norma Fox ◽  
Kenneth Kaushansky
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Hematopoietic Stem Cells ◽  
Nuclear Translocation ◽  
Hematopoietic Cells ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Hematopoietic Stem ◽  
Nuclear Localization Signals ◽  
Mitogen Activated Protein

ABSTRACT Members of the homeobox family of transcription factors are major regulators of hematopoiesis. Overexpression of either HOXB4 or HOXA9 in primitive marrow cells enhances the expansion of hematopoietic stem cells (HSCs). However, little is known of how expression or function of these proteins is regulated during hematopoiesis under physiological conditions. In our previous studies we demonstrated that thrombopoietin (TPO) enhances levels of HOXB4 mRNA in primitive hematopoietic cells (K. Kirito, N. Fox, and K. Kaushansky, Blood 102:3172-3178, 2003). To extend our studies, we investigated the effects of TPO on HOXA9 in this same cell population. Although overall levels of the transcription factor were not affected, we found that TPO induced the nuclear import of HOXA9 both in UT-7/TPO cells and in primitive Sca-1+/c-kit+/Gr-1− hematopoietic cells in a mitogen-activated protein kinase-dependent fashion. TPO also controlled MEIS1 expression at mRNA levels, at least in part due to phosphatidylinositol 3-kinase activation. Collectively, TPO modulates the function of HOXA9 by leading to its nuclear translocation, likely mediated by effects on its partner protein MEIS1, and potentially due to two newly identified nuclear localization signals. Our data suggest that TPO controls HSC development through the regulation of multiple members of the Hox family of transcription factors through multiple mechanisms.

scholarly journals Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1293 ◽  
Author(s):  
Ghmkin Hassan ◽  
Masaharu Seno
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Cells ◽  
Solid Tumor ◽  
Immune Cells ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Tumor Microenvironments

The concepts of hematopoiesis and the generation of blood and immune cells from hematopoietic stem cells are some steady concepts in the field of hematology. However, the knowledge of hematopoietic cells arising from solid tumor cancer stem cells is novel. In the solid tumor microenvironment, hematopoietic cells play pivotal roles in tumor growth and progression. Recent studies have reported that solid tumor cancer cells or cancer stem cells could differentiate into hematopoietic cells. Here, we discuss efforts and research that focused on the presence of hematopoietic cells in tumor microenvironments. We also discuss hematopoiesis from solid tumor cancer stem cells and clarify the notion of differentiation of solid tumor cancer stem cells into non-cancer hematopoietic stem cells.

scholarly journals TGF-β1 Negatively Regulates the Number and Function of Hematopoietic Stem Cells

2018 ◽  
Vol 11 (1) ◽  
pp. 274-287 ◽  
Author(s):  
Xiaofang Wang ◽  
Fang Dong ◽  
Sen Zhang ◽  
Wanzhu Yang ◽  
Wenying Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
And Function ◽  
Tgf Β1

scholarly journals Negative Regulation of the Differentiation of Flk2− CD34− LSK Hematopoietic Stem Cells by EKLF/KLF1

2020 ◽  
Vol 21 (22) ◽  
pp. 8448
Author(s):  
Chun-Hao Hung ◽  
Keh-Yang Wang ◽  
Yae-Huei Liou ◽  
Jing-Ping Wang ◽  
Anna Yu-Szu Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Gene Knockout ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Interesting Correlation ◽  
Regulatory Effects ◽  
High Level

Erythroid Krüppel-like factor (EKLF/KLF1) was identified initially as a critical erythroid-specific transcription factor and was later found to be also expressed in other types of hematopoietic cells, including megakaryocytes and several progenitors. In this study, we have examined the regulatory effects of EKLF on hematopoiesis by comparative analysis of E14.5 fetal livers from wild-type and Eklf gene knockout (KO) mouse embryos. Depletion of EKLF expression greatly changes the populations of different types of hematopoietic cells, including, unexpectedly, the long-term hematopoietic stem cells Flk2− CD34− Lin− Sca1+ c-Kit+ (LSK)-HSC. In an interesting correlation, Eklf is expressed at a relatively high level in multipotent progenitor (MPP). Furthermore, EKLF appears to repress the expression of the colony-stimulating factor 2 receptor β subunit (CSF2RB). As a result, Flk2− CD34− LSK-HSC gains increased differentiation capability upon depletion of EKLF, as demonstrated by the methylcellulose colony formation assay and by serial transplantation experiments in vivo. Together, these data demonstrate the regulation of hematopoiesis in vertebrates by EKLF through its negative regulatory effects on the differentiation of the hematopoietic stem and progenitor cells, including Flk2− CD34− LSK-HSCs.

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