scholarly journals ARID1A Is Critical for Maintaining Normal Hematopoiesis in Mice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3833-3833
Author(s):  
Lin Han ◽  
Vikas Madan ◽  
Anand Mayakonda ◽  
Pushkar Dakle ◽  
Weoi Woon Teoh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Chromatin Remodeling ◽  
B Cell Lymphoma ◽  
Chromatin Accessibility ◽  
Brdu Incorporation ◽  
Rna Seq ◽  
Hematopoietic Stem ◽  
Hematopoietic Development

Abstract ARID1A is a key component of ATP-dependent SWI/SNF complex involved in chromatin remodeling. Chromatin remodeling mediated by SWI/SNF complex is crucial for gene expression and affects a broad range of biological processes including hematopoietic development. ARID1A is frequently mutated across several solid tumors as well as hematopoietic malignancies, including Burkitt's lymphoma, diffuse large B-cell lymphoma and acute promyelocytic leukemia. Nevertheless, function of ARID1A in adult hematopoiesis and implications of its deficiency in development and progression of hematopoietic diseases has not been explored. In this study, we used a murine model of ARID1A deficiency to establish its essential function in maintaining normal hematopoietic development. Germline loss of Arid1a is embryonic lethal; therefore, we generated mice with deletion of Arid1a specifically in the hematopoietic compartment using Vav-iCre and Mx1-Cre transgenic mice. Arid1afl/fl;Vav-iCre+ mice occurred at a lower than expected frequency, suggesting some perinatal mortality. For the Mx1-Cre model, Arid1a exon 9 was excised by administrating poly(I:C) to adult mice and hematopoiesis was evaluated using flow cytometry. An increase in both percentage and absolute number of long-term hematopoietic stem cells (LTHSCs) defined as Lin-Sca1+Kit+CD34-FLT3- or Lin-Sca1+Kit+CD48-CD150+ occurred in the bone marrow using both models of Arid1a deficiency. RNA-sequencing of sorted LTHSCs from Arid1a KO bone marrow revealed dysregulated expression of several genes involved in cell cycle, G2/M checkpoint and related pathways. In vivo BrdU incorporation assays showed a substantially lower proportion of quiescent hematopoietic stem cells in Arid1a deficient bone marrow. To assess the reconstitution ability of ARID1A deficient HSCs, sorted KO or WT LTHSCs were transplanted into irradiated congenic recipient mice in competitive repopulation assays. Proportion of donor-derived cells in recipients transplanted with KO cells was strikingly lower compared to wild-type cells, suggesting poor reconstitution ability of Arid1a KO LTHSCs. Also, differentiation of both myeloid and lymphoid lineages was impaired in Arid1a KO mice compared to WT controls. To investigate the mechanism of perturbed differentiation of the myeloid and erythroid lineages, RNA-Seq was performed on sorted CMPs, GMPs and MEPs from WT and Arid1a KO BM. Our analysis showed significant decrease in expression of several transcription factors (Runx1, Gata2, Cebpa), which play a crucial role in lineage differentiation. To determine how Arid1a deficiency alters chromatin accessibility in myeloid precursors, Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-Seq) was performed on sorted Lin-Kit+ BM cells from both Arid1a KO and WT mice. A global reduction in open chromatin in Arid1a KO cells was noted compared to WT cells. A substantial overlap occurred between down regulated genes (RNA-seq) and reduced chromatin accessibility in Arid1a KO myeloid progenitors. Motifs for PU.1, RUNX1, GATA and CEBPA were significantly enriched in loci with reduced ATAC-seq signals in Arid1a KO cells. Our findings demonstrate an indispensable function of Arid1a in hematopoietic development and underline the importance of precise chromatin dynamics maintained by ARID1A-containing SWI/SNF complex in hematopoiesis. Disclosures No relevant conflicts of interest to declare.

Multifunctional Role of Caspase-3 in Regulating Hematopoietic Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 861-861 ◽  
Author(s):  
Viktor Janzen ◽  
Heather E. Fleming ◽  
Michael T. Waring ◽  
Craig D. Milne ◽  
David T. Scadden
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Brdu Incorporation ◽  
Hematopoietic Stem ◽  
Regulatory Pathways

Abstract The processes of cell cycle control, differentiation and apoptosis are closely intertwined in controlling cell fate during development and in adult homeostasis. Molecular pathways connecting these events in stem cells are poorly defined and we were particularly interested in the cysteine-aspartic acid protease, Caspase-3, an ‘executioner’ caspase also implicated in the regulation of the cyclin dependent kinase inhibitors, p21Cip1 and p27Kip1. These latter proteins are known to participate in primitive hematopoietic cell cycling and self-renewal. We demonstrated high levels of Caspase-3 mRNA and protein in immunophenotypically defined mouse hematopoietic stem cells (HSC). Using mice engineered to be deficient in Caspase-3, we observed a consistent reduction of lymphocytes in peripheral blood counts and a slight reduction in bone marrow cellularity. Notably, knockout animals had an increase in the stem cell enriched Lin−cKit+Sca1+Flk2low (LKSFlk2lo) cell fraction. The apoptotic rates of LKS cells under homeostatic conditions as assayed by the Annexin V assay were not significantly different from controls. However, in-vitro analysis of sorted LKS cells revealed a reduced sensitivity to apoptotic cell death in absence of Caspase-3 under conditions of stress (cytokine withdrawal or gamma irradiation). Primitive hematopoietic cells displayed a higher proliferation rate as demonstrated by BrdU incorporation and a significant reduction in the percentage of cells in the quiescent stage of the cell cycle assessed by the Pyronin-Y/Hoechst staining. Upon transplantation, Caspase-3−/− stem cells demonstrated marked differentiation abnormalities with significantly reduced ability to differentiate into multiple hematopoietic lineages while maintaining an increased number of primitive cells. In a competitive bone marrow transplant using congenic mouse stains Capase-3 deficient HSC out-competed WT cells at the stem cell level, while giving rise to comparable number of peripheral blood cells as the WT controls. Transplant of WT BM cells into Caspase-3 deficient mice revealed no difference in reconstitution ability, suggesting negligible effect of the Caspase-3−/− niche microenvironment to stem cell function. These data indicate that Caspase-3 is involved in the regulation of differentiation and proliferation of HSC as a cell autonomous process. The molecular bases for these effects remain to be determined, but the multi-faceted nature of the changes seen suggest that Caspase-3 is central to multiple regulatory pathways in the stem cell compartment.

FLT3 Internal Tandem Duplication (ITD) Mutations Disrupt Homeostasis in Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1420-1420
Author(s):  
S. Haihua Chu ◽  
Diane Heiser ◽  
Li Li ◽  
Ian M Kaplan ◽  
Curt I. Civin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Tandem Duplication ◽  
Brdu Incorporation ◽  
Myeloproliferative Disease ◽  
Internal Tandem Duplication ◽  
Hematopoietic Stem ◽  
Activating Mutations

Abstract Abstract 1420 Poster Board I-443 As one of the most common genetic alterations found in acute myeloid leukemia (AML), constitutive activation of the FMS-like tyrosine kinase (FLT3) has provided a promising candidate for small molecule targeted therapy. However, the results of FLT3 inhibitor monotherapy trials indicate FLT3 inhibition alone is insufficient to induce consistent and durable responses. Moreover, after an initial response, many patients relapse, suggesting that leukemia-initiating stem cells may be escaping inhibitor-induced cytotoxicity. Currently, the exact stage at which activating mutations in FLT3 occur during transformation is unknown. While FLT3 knockout mice have minor defects in hematopoiesis, very little is known about either the effect of FLT3 activating mutations on normal hematopoietic stem cells or the contribution of FLT3 activation to leukemogenesis. Thus, in order to better understand the underlying molecular mechanisms of transformation and to identify novel targets for treatment of AML, the role of FLT3 activating mutations in hematopoietic stem cells (HSCs) is of great interest. To study the natural stem cell reservoir and other populations that may escape inhibition, our laboratory has developed a knock-in mouse model in which the FLT3/ITD mutation (an internal tandem duplication correlated with poor prognosis in patients) has been introduced under the endogenous promoter, resulting in myeloproliferative disease (MPD). Conventional transplantation using unfractionated or lineage-depleted marrow from FLT3/ITD mice failed to fully engraft or recapitulate disease, suggesting a HSC defect. Thus, in order to identify a compartment enriched for MPD-initiating cells, several cell surface marker-defined hematopoietic populations were transplanted and compared for engraftment and disease recapitulation. Lineage negative (LIN-), KSL (KIT+SCA+LIN-), MPP (KSL CD34+FLT3+), and ST-HSC (KSL CD34+FLT3-) cells sorted from FLT3/ITD bone marrow all had significantly reduced reconstitution capacity compared to the same compartment from WT littermates. In contrast, highly purified LT-HSCs (KSL CD34-FLT3-) generated equivalent engraftment whether from WT or ITD bone marrow. Furthermore, we measured Hoechst dye efflux in WT and ITD bone marrow to examine side population (SP) cells, known to be enriched in HSC activity, and found that FLT3/ITD mice displayed five-fold fewer SP cells. In addition, bone marrow from FLT3/ITD mice showed a ten-fold decrease in SLAM-defined stem cell frequency (LIN-CD48-CD41-CD150+). 500 sorted SLAM cells from either WT or FLT3/ITD mice were sufficient to fully reconstitute a transplant recipient, demonstrating an equivalent engraftment capacity within this HSC-enriched compartment. Moreover, the MPD phenotype was successfully recapitulated in primary transplants of FLT3/ITD SLAM cells as characterized by an increase in myeloid progenitors, expansion of the LIN- fraction, enlarged spleens and depletion of the SLAM compartment compared to WT SLAM transplant recipients. Classically defined as a class II oncogene, FLT3 activating mutations have been shown to drive proliferation in cells harboring the mutation. To investigate whether FLT3/ITD drives proliferation in the most primitive hematopoietic compartments, BrdU incorporation was examined in FLT3/ITD hematopoietic stem and progenitor-enriched subsets. While myeloid progenitor compartments showed a decrease in proliferation as compared to WT littermates, the FLT3/ITD SLAM and KSL compartments had an increased percentage of BrdU-incorporating cells. Altogether, our data suggests a role for FLT3/ITD in driving normally quiescent HSCs to proliferate, thereby depleting the pool of primitive HSCs. In this model, HSC depletion coupled to rapid expansion in progenitor cell numbers leads to perturbation of normal hematopoiesis giving rise to a myeloproliferative disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1590-1600 ◽  
Author(s):  
Hiromi Iwasaki ◽  
Chamorro Somoza ◽  
Hirokazu Shigematsu ◽  
Estelle A. Duprez ◽  
Junko Iwasaki-Arai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
B Cells ◽  
Hematopoietic Stem Cells ◽  
B Cell ◽  
Cell Maturation ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
B Cell Maturation ◽  
Lymphoid Progenitors

Abstract The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent “priming” of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages.

scholarly journals Hematopoietic Jagged1 Is Required for the Transition of Hematopoietic Stem Cells from the Fetal Liver to the Adult Bone Marrow Niche

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Lijian Shao ◽  
Na Yoon Paik ◽  
Kostandin V. Pajcini
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Hematopoietic Stem Cells ◽  
Notch Signaling ◽  
Fetal Liver ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Adult Bone Marrow ◽  
Adult Bone

Notch signaling is known to play important roles in hematopoietic development and differentiation. Notch1 is required for emergence of the definitive hematopoietic stem cells (HSCs) from the hemogenic endothelium, and we have previously shown that Notch signaling is essential for survival and function of HSCs in the fetal liver. Activation of canonical Notch signaling requires direct cellular contact; thus, the identity of the ligand and the ligand-presenting cell during hematopoietic development would provide valuable information of the Notch signaling mechanism in HSCs as well as the identity of key niche cells that drive the expansion and cell fate decisions of embryonic HSCs. In the present study, we have taken a comprehensive approach to determine the ligands and cells that initiate Notch signaling in the mouse fetal liver. To this end, we have performed single-cell PCR analysis for all Notch signaling proteins in E14.5 fetal HSCs and compared the findings to the adult bone marrow HSCs. We also have analyzed fetal liver endothelial cells for surface expression of all Notch ligands. We determined that Jagged1 (Jag1) is highly expressed in both endothelial cells as well as in fetal HSCs but not adult HSCs. We have performed conditional loss-of-function analysis of Jag1 in fetal endothelial cells using inducible Ve-cadherinCreERT2 as well as in fetal hematopoietic lineages using constitutive VavCre. Our results indicate that while loss of endothelial Jag1 has severe effects in embryonic vascular development, loss of hematopoietic Jag1 allows for normal fetal morphology, yet severely impedes the functional ability of fetal liver HSCs to expand and differentiate both in vitro and in vivo. Fetal to adult transplantation of VavCre+Jag1f/f HSCs indicated a defect in reconstitution potential of fetal HSCs that lack Jag1 expression. Our findings indicate that hematopoietic Jag1 is essential for maturation of HSCs in the fetal liver and for homing and reconstitution potential of HSCs into the post-natal bone marrow microenvironment. Disclosures No relevant conflicts of interest to declare.

Toll-Like Receptor (TLR) Signaling Adaptor Protein MYD88 in Myelodysplastic Syndromes (MDS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 556-556
Author(s):  
Sophie Dimicoli ◽  
Yue Wei ◽  
Rui Chen ◽  
Carlos E. Bueso-Ramos ◽  
Sherry A. Pierce ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Innate Immunity ◽  
Hematopoietic Stem Cells ◽  
Myelodysplastic Syndromes ◽  
Adaptor Protein ◽  
B Cell Lymphoma ◽  
Toll Like Receptor ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract Abstract 556 We have documented that deregulation of the Toll-like Receptor 2 (TLR2) centered innate immunity signals contribute to the pathogenesis of myelodysplastic syndromes (MDS). Of relevance, oncogenically active mutations of MYD88, a signal adaptor protein for TLR signal, have recently been identified as recurrent genetic lesions in both B-cell lymphoma and in chronic lymphocytic leukemia (CLL) (Vu N et al. Nature 2010 and Puente et al. Nature 2011). This information further supports the importance of innate immunity deregulation in leukemogenesis. To further characterize this pathway in MDS, we analyzed potential genetic alteration and expression level of MYD88 in patients of MDS. In a cohort of 40 MDS whole bone marrow mononuclear cell DNA, we first performed pyrosequencing analysis focusing on a list of previously reported MYD88 mutations (V217, W218, S219, I220, S222, M232, S243, L265, and T294). We did not detect mutation of any these hotspots on MYD88 in MDS. We then expanded the sequencing efforts to the entire coding region of MYD88 using an approach that combines PCR amplification and massive parallel sequencing. Still, no mutation of MYD88 was detected using this technique. We then examined the expression of MYD88 in CD34+ hematopoietic stem cells from 65 patients with MDS. In comparison to healthy donors, 26% of MDS patients (N=17) presented a more than 2 fold increase of MYD88 RNA, and 15% (N=10) had a 30%–90% increase. In average, MYD88 RNA level was 1.7 fold increased compared to control. Of potential clinical relevance, patients with higher MYD88 RNA expression in bone marrow CD34+ cells (above median value) (N=33) had a propensity of shorter period (24.4 mo) of overall survival (OS) in comparison to patients with lower levels of MYD88 expression (N=32) (32 mo)(P=0.05). We also found that patients with higher levels of MYD88 expression (split at 0.8 fold to controls) tended to have higher WBC (P=0.02). We have previously shown that blockade of the TLR2 mediated innate immunity signaling in MDS CD34+ cells could positively regulate erythroid lineage differentiation. To evaluate the potential of MYD88 blockade, we applied a 26 AA MYD88 inhibitory peptide that blocks its homodimerization (Invivogen, San Diego, CA) on primary CD34+ cells isolated from patients with lower-risk MDS (N=5). Methylcellulose medium supported colony formation assays indicated that the presence of MYD88 inhibitor led to an average of 60% increase for the numbers of erythroid colonies and a 30% increase for the numbers of total colonies. At the same time, we did not observe these effects of MYD88 blockade on the CD34+ cells isolated from the patients of higher-risk MDS (N=3). IL-8 is one of the key downstream transcriptional targets of the TLR-MYD88-NFkB innate immunity signaling that was documented to be elevated in bone marrow plasma of MDS. ELISA assays also indicated that blockade MYD88 in cultured MDS CD34+ cells led to a decrease of IL-8 concentration in medium. Taken together, these results indicated that MYD88 is overexpressed in hematopoietic stem cells of MDS and that blockade of MYD88 mediated innate immunity signaling may have therapeutic potential in treating patients with MDS. Disclosures: Kantarjian: Genzyme: Research Funding.

scholarly journals Alterations in Secretome and Transcriptome of Bone Marrow Derived MSCs in Patients with Diffuse Large B-Cell Lymphoma without Bone Marrow Involvement

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1514-1514
Author(s):  
Nataliya A. Petinati ◽  
Natalia Sats ◽  
Nina J. Drize ◽  
Irina Malyants ◽  
Victoria Shender ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Complete Remission ◽  
Hematopoietic Stem Cells ◽  
Signaling Pathways ◽  
B Cell Lymphoma ◽  
Ion Source ◽  
Phenol Red ◽  
Hematopoietic Stem ◽  
Healthy Donors

Introduction Multipotent mesenchymal stromal cells (MSCs) differentiate into all mesenchymal lineages, regulate hematopoietic stem cells, and also take part in immunomodulation. MSCs are damaged in patients with leukemia. Most of the patients with DLBCL do not have bone marrow (BM) involvement. Despite the absence of proved BM damage in DLBCL patients, the properties of MSCs are changed. We aimed to analyze secretome and transcriptome of MSCs derived from BM of DLBCL patients without BM involvement. Methods The study included 16 DLBCL patients (7 males and 9 females), of which 6 were 42-60-year-old in the onset of the disease and a month after the end of treatment with NHL-BFM90; 10 were 48-78-year-old in complete remission for 6-14 years (5 received CHOP and 5 NHL-BFM90 treatment). Control group included 5 healthy donors (3 males, 2 females), median age 37. During diagnostic punctures BM was collected after informed consent. MSCs were cultured by standard method. Confluent MSCs layers after 1 passage were cultivated in serum-free RPMI1640 without phenol red for 24 hours; supernatants were studied for secretome and cells for transcriptome. The analysis of MSCs secretome was carried out using the LC-MS/MS analysis (TripleTOF 5600+ mass spectrometer with a NanoSpray III ion source coupled to a NanoLC Ultra 2D+ nano-HPLC System. Total RNA was isolated, applying standard procedures, from MSCs. Next-generation sequencing of complementary DNA libraries of polyA-enriched RNA was performed with Illumina HiSeq. Raw RNA-seq data were processed using STAR. Gene expression was compared using the limma R/Bioconductor package. Results The total cell production for 4 passages in primary patients' MSCs was higher than in donors (26.6 ± 2 versus 10.1 ± 4.4 x 106 per flask). It remained elevated regardless of the time passed after therapy. The patterns of secretome and transcriptome of patients' MSCs differed dramatically from the MSCs of healthy donors (Table). In MSCs of primary patients, the secretion and transcription of proteins involved in IL-17, TNF and Toll-like receptor signaling pathways, cytokine-cytokine receptor interaction, cytokine-mediated signaling pathway, cellular response to cytokine stimulus, regulation of signaling receptor activity, regulation of neutrophil chemotaxis, inflammatory and acute inflammatory response and its regulation, leukocyte activation involved in immune response, immune system process, extracellular matrix organization were elevated. Secretion and transcription of cytokines and chemokines (IL6, IL4, LIF, TNFa, CXCL1 and CXCL3), taking part in hematopoiesis regulation were increased in primary patients MSCs. One month after treatment, secretion of 332 proteins was decreased, only 2 of them (DKK1 and FKBP7) were previously overexpressed in primary patients. Many years after the end of both variants of treatment, the secretion and transcription of 32 proteins participating in the same pathways as before treatment remains elevated compared with healthy donors. In addition, the complement and coagulation cascades became upregulated. In MSCs of all patients, regardless of therapy and remission duration , expression/ secretion of following genes/proteins: ACAN, COL1A, MMP3, TGFb1, NDNF, CANX, LAP3, MGP, SERPINB2, STC1,TFPI,TMEM132A, BMP2, CFH, HILPDA, IDO1, IL1B, ITGA2, JUN, LMO2, MMP13, MMP3, TNFRSF1B,TNFSF4 was increased. Some of these proteins take part in bone and cartilage formation, hematopoietic stem cells regulation, blood coagulation and inflammation. These changes in secreted proteins reflect the response of MSCs at the organism level to the tumor presence. Moreover, NUCKS1 overexpression was observed in MSCs of all patients. This nuclear casein kinase plays a significant role in modulating chromatin structure and regulates replication, transcription, and chromatin condensation. Furthermore, this protein contributes to the susceptibility, occurrence, and development of several types of cancer and other diseases. NUCKS1 is considered to be a potent marker for such diseases. Conclusion The presence of a lymphoid tumor without BM involvement in the body leads to irreversible changes in the BM MSCs, thus affecting a lot of biological processes and signaling pathways, independent of the treatment and duration of complete remission. The work were supported by the Russian Foundation for Basic Research, Project No. 17-00-00170. Disclosures No relevant conflicts of interest to declare.

The Impact of Age and Gender on Hematopoietic Stem Cells and Immune Contexture of the Bone Marrow Microenvironment

2020 ◽  
pp. 1-6
Author(s):  
Rebar N. Mohammed
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Immune Cells ◽  
Absolute Number ◽  
Cell Number ◽  
Hematopoietic Stem ◽  
The Absolute ◽  
And Gender ◽  
The Impact

Hematopoietic stem cells (HSCs) are a rare population of cells that reside mainly in the bone marrow and are capable of generating and fulfilling the entire hematopoietic system upon differentiation. Thirty-six healthy donors, attending the HSCT center to donate their bone marrow, were categorized according to their age into child (0–12 years), adolescence (13–18 years), and adult (19–59 years) groups, and gender into male and female groups. Then, the absolute number of HSCs and mature immune cells in their harvested bone marrow was investigated. Here, we report that the absolute cell number can vary considerably based on the age of the healthy donor, and the number of both HSCs and immune cells declines with advancing age. The gender of the donor (male or female) did not have any impact on the number of the HSCs and immune cells in the bone marrow. In conclusion, since the number of HSCs plays a pivotal role in the clinical outcome of allogeneic HSC transplantations, identifying a younger donor regardless the gender is critical.

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