scholarly journals Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Christian A. Di Buduo ◽  
Maria Adele Alberelli ◽  
Ana C. Glembotsky ◽  
Gianmarco Podda ◽  
Paola R. Lev ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Hematopoietic Progenitor Cells ◽  
Loss Of Function ◽  
Hematopoietic Progenitor ◽  
Autosomal Recessive Form ◽  
Recessive Form ◽  
Gray Platelet Syndrome ◽  
Marrow Fibrosis ◽  
Platelet Formation

Abstract The Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by deficiency of platelet α-granules, macrothrombocytopenia and marrow fibrosis. The autosomal recessive form of GPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule trafficking in megakaryocytes, the platelet progenitors. We report the first analysis of cultured megakaryocytes from GPS patients with NBEAL2 mutations. Megakaryocytes cultured from peripheral blood or bone marrow hematopoietic progenitor cells from four patients were used to investigate megakaryopoiesis, megakaryocyte morphology and platelet formation. In vitro differentiation of megakaryocytes was normal, whereas we observed deficiency of megakaryocyte α-granule proteins and emperipolesis. Importantly, we first demonstrated that platelet formation by GPS megakaryocytes was severely affected, a defect which might be the major cause of thrombocytopenia in patients. These results demonstrate that cultured megakaryocytes from GPS patients provide a valuable model to understand the pathogenesis of GPS in humans.

scholarly journals Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In Vitro

Immunity ◽  
2002 ◽  
Vol 17 (6) ◽  
pp. 749-756 ◽  
Author(s):  
Thomas M. Schmitt ◽  
Juan Carlos Zúñiga-Pflücker
Keyword(s):  
T Cell ◽  
Progenitor Cells ◽  
T Cell Development ◽  
Cell Development ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor

scholarly journals DJ-1 regulates the integrity and function of ER-mitochondria association through interaction with IP3R3-Grp75-VDAC1

2019 ◽  
Vol 116 (50) ◽  
pp. 25322-25328 ◽  
Author(s):  
Yi Liu ◽  
Xiaopin Ma ◽  
Hisashi Fujioka ◽  
Jun Liu ◽  
Shengdi Chen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cellular Mechanism ◽  
Loss Of Function ◽  
Wild Type ◽  
Calcium Efflux ◽  
And Function ◽  
The Brain ◽  
Early Onset Parkinson’S Disease

Loss-of-function mutations in DJ-1 are associated with autosomal recessive early onset Parkinson’s disease (PD), yet the underlying pathogenic mechanism remains elusive. Here we demonstrate that DJ-1 localized to the mitochondria-associated membrane (MAM) both in vitro and in vivo. In fact, DJ-1 physically interacts with and is an essential component of the IP3R3-Grp75-VDAC1 complexes at MAM. Loss of DJ-1 disrupted the IP3R3-Grp75-VDAC1 complex and led to reduced endoplasmic reticulum (ER)-mitochondria association and disturbed function of MAM and mitochondria in vitro. These deficits could be rescued by wild-type DJ-1 but not by the familial PD-associated L166P mutant which had demonstrated reduced interaction with IP3R3-Grp75. Furthermore, DJ-1 ablation disturbed calcium efflux-induced IP3R3 degradation after carbachol treatment and caused IP3R3 accumulation at the MAM in vitro. Importantly, similar deficits in IP3R3-Grp75-VDAC1 complexes and MAM were found in the brain of DJ-1 knockout mice in vivo. The DJ-1 level was reduced in the substantia nigra of sporadic PD patients, which was associated with reduced IP3R3-DJ-1 interaction and ER-mitochondria association. Together, these findings offer insights into the cellular mechanism in the involvement of DJ-1 in the regulation of the integrity and calcium cross-talk between ER and mitochondria and suggests that impaired ER-mitochondria association could contribute to the pathogenesis of PD.

scholarly journals Gene transfer of multidrug resistance into a factor-dependent human hematopoietic progenitor cell line: in vivo model for genetically transferred chemoprotection

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2723-2731 ◽  
Author(s):  
P Schwarzenberger ◽  
S Spence ◽  
N Lohrey ◽  
T Kmiecik ◽  
DL Longo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Gene Transfer ◽  
Hematopoietic Progenitor Cells ◽  
Mdr1 Gene ◽  
In Vivo Model ◽  
Hematopoietic Progenitor ◽  
Human Dna

To develop a rapid preclinical in vivo model to study gene transfer into human hematopoietic progenitor cells, MO-7e cells (CD-34+, c-kit+) were infected with multidrug resistance (MDR1)-containing retroviruses and then transplanted into nonobese diabetic severe combined immunodeficient mice (NOD SCID). MO-7e cells infected with a retrovirus encoding the human MDR1 cDNA showed integration, transcription, and expression of the transfered MDR1 gene. This resulted in a 20-fold increase in the resistance of MO-7e cells to paclitaxel in vitro. The expression of the MDR1 gene product was stable over a 6-month period in vitro without selection in colchicine. MO-7e and MDR1-infected MO-7e cells were transplanted into NOD SCID mice to determine whether MDR1 could confer drug resistance in vivo. A sensitive polymerase chain reaction method specific for human sequences was developed to quantitate the level of human cell engraftment in NOD SCID bone marrow (BM) cells. The percentage of human DNA in BM cells from MO-7e- transplanted mice was 10.9% and decreased to 0.7% in mice treated with paclitaxel. The percentage of human DNA in infected-MO-7e transplanted mice was 7.6% and that level was unchanged in mice treated with paclitaxel. These results show that expression of the MDR1 gene in human hematopoietic progenitor cells can confer functional drug resistance in an in vivo model.

ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency

Science ◽  
1994 ◽  
Vol 264 (5165) ◽  
pp. 1599-1601 ◽  
Author(s):  
A. Chan ◽  
T. Kadlecek ◽  
M. Elder ◽  
A. Filipovich ◽  
W. Kuo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Autosomal Recessive Form ◽  
Recessive Form

scholarly journals Preferential sequestration in vitro of BCR/ABL negative hematopoietic progenitor cells among cytokine nonresponsive CML marrow CD34+ cells

1997 ◽  
Vol 19 (12) ◽  
pp. 1213-1221 ◽  
Author(s):  
P Veena ◽  
K Cornetta ◽  
A Davidson ◽  
B Agüero ◽  
J McMahel ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells

Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal recessive form

2004 ◽  
Vol 9 (2) ◽  
pp. 122-123 ◽  
Author(s):  
ML Mostacciuolo ◽  
E Crestanello ◽  
F Boaretto ◽  
E Boscolo ◽  
M Liguori ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Motor Neuropathy ◽  
Hereditary Motor ◽  
Autosomal Recessive Form ◽  
Recessive Form ◽  
Hereditary Motor Neuropathy

Respiratory insufficiency in a severe autosomal recessive form of musclar dystrophy

1984 ◽  
Vol 4 (1) ◽  
pp. 45-48 ◽  
Author(s):  
Mustafa Abdalla M. Salih ◽  
Assadour Ekmejian ◽  
Mohamed Ibrahim A. Omer
Keyword(s):  
Respiratory Insufficiency ◽  
Autosomal Recessive ◽  
Autosomal Recessive Form ◽  
Recessive Form

scholarly journals An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation

2006 ◽  
Vol 140A (14) ◽  
pp. 1504-1510 ◽  
Author(s):  
Anna Rajab ◽  
Seung-Yun Yoo ◽  
Aiman Abdulgalil ◽  
Salem Kathiri ◽  
Riaz Ahmed ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Mental Retardation ◽  
Autosomal Recessive ◽  
Spastic Cerebral Palsy ◽  
Autosomal Recessive Form ◽  
Recessive Form
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