Blood and immune development in human fetal bone marrow and Down syndrome

Nature ◽  
2021 ◽  
Author(s):  
Laura Jardine ◽  
Simone Webb ◽  
Issac Goh ◽  
Mariana Quiroga Londoño ◽  
Gary Reynolds ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Down Syndrome ◽  
Immune Development ◽  
Fetal Bone

Trisomy 21 Expands the Megakaryocyte-Erythroid Progenitor Compartment in Human Fetal Liver-Implications for Down Syndrome AMKL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 563-563 ◽  
Author(s):  
Oliver Tunstall-Pedoe ◽  
Josu de la Fuente ◽  
Phillip R. Bennett ◽  
Nicholas M. Fisk ◽  
Paresh Vyas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Down Syndrome ◽  
Trisomy 21 ◽  
Fetal Liver ◽  
Fetal Blood ◽  
Fetal Bone ◽  
Cd34 Cells ◽  
Progenitor Compartment ◽  
Gata1 Mutation

Abstract Children with Down syndrome (DS) have a uniquely high frequency of acute megakaryoblastic leukemia (AMKL)- ~500-fold increased compared to children without trisomy 21 (T21). At least two genetic events are required but are not sufficient for DS-AMKL: T21 and N-terminal truncating mutations in the key megakaryocytic transcription factor GATA1. This tight association of T21 with GATA1 mutations and the development of AMKL in a narrow temporal window (fetal life-5yrs) makes DS-AMKL a highly informative model of multi-hit leukemogenesis in which the first steps occur in utero. However, the individual contributions of T21 and mutant GATA1 in the leukemogenesis are unclear. To specifically investigate the role of T21 in DS-AMKL and why leukemia-initiation is confined to fetal (or early post-natal) life we have studied fetal hemopoiesis in DS during the second and third trimester in 16 fetuses (gestational age 15–37 weeks) where an antenatal diagnosis of DS with T21 was made by amniotic fluid fetal cell karyotyping. Samples of fetal blood (n=13), fetal liver (n=9) and fetal bone marrow (n=8) were screened for mutations in the GATA1 gene genomic DNA by DHPLC or direct sequencing (sensitivity of detecting a GATA1 mutation is 1–5% by DHPLC). No GATA1 mutations were detected. This allowed us to study the impact of T21 independent of GATA1 mutation on fetal hemopoiesis. DS fetuses showed marked qualitative and quantitative abnormalities in hemopoiesis. While the total number of CD34+ cells in DS and normal fetal liver were comparable, DS fetuses had a striking increase in bi-potential megakaryocyte-erythroid progenitors (MEP; CD34+CD38+FcgloCD45RA+− 74.4% vs 27.0% of fetal liver CD34+/CD38+ cells. Peripheral blood from all DS fetuses studied compared to normal fetal blood samples showed dysmegakaryopoiesis (abnormally shaped and/or giant platelets and MK fragments), dyserythropoiesis (macrocytes, poikilocytes, basophilic stippling), increased numbers of blast cells and also had an increased percentage of MEPs − 40.3% vs 26.9%. By contrast, there was no difference in the number of MEP nor erythroid or MK lineage morphology in DS fetal bone marrow compared to normal fetal bone marrow. CD34+ cells from DS fetal liver and fetal blood expressed both fl GATA1 and GATA1s mRNA indicating that dysmegakaryopoiesis and erythropoiesis were not due to lack of expression of fl GATA1. These data indicate, for the first time, that T21 by itself profoundly disturbs megakaryopoiesis and erythropoiesis and leads to an increased of frequency of MEP. This has important implications since it provides a testable hypothesis for the role of T21 in the initiating step of AMKL, namely that T21 expands a fetal liver-derived progenitor compartment which forms a substrate upon which GATA1 mutations then confer a further selective advantage.

Myelodysplastic Syndrome, Myeloid Leukaemia of Down Syndrome, and Juvenile Myelomonocytic Leukaemia

2020 ◽  
pp. 134-141
Author(s):  
Henrik Hasle ◽  
Charlotte M. Niemeyer
Keyword(s):  
Bone Marrow ◽  
Down Syndrome ◽  
Stem Cell ◽  
Acute Myeloid Leukaemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukaemia ◽  
Clinical Characteristics ◽  
Bone Marrow Failure ◽  
Signal Pathways ◽  
Acute Myeloid

Myeloid malignancies in children are divided into acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS), juvenile myelomonocytic leukaemia (JMML), and the myeloid leukaemia of Down syndrome (ML-DS). Predisposing genetic conditions are common in MDS. Differentiating MDS from inherited bone marrow failure or AML may be challenging. Therapy consists of observation, immunosuppression, or stem-cell transplantation (SCT). Germline and somatic mutations deregulating the Ras/MAPK signal pathways are key initiating events in JMML. Genetics in JMML defines clinically relevant subgroups and indications for SCT. ML-DS presents with unique clinical characteristics and responds favourably to reduced doses of AML chemotherapy; however, relapse is often refractory to therapy.

Immunomodulatory and immunogenic properties of mesenchymal stem cells derived from bovine fetal bone marrow and adipose tissue

2019 ◽  
Vol 124 ◽  
pp. 212-222 ◽  
Author(s):  
Olger Huaman ◽  
Javiera Bahamonde ◽  
Berly Cahuascanco ◽  
Miguel Jervis ◽  
Jaime Palomino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Fetal Bone ◽  
Immunogenic Properties

scholarly journals Identification of novel B-lineage cells in human fetal bone marrow that coexpress CD7 [see comments]

Blood ◽  
1991 ◽  
Vol 77 (1) ◽  
pp. 64-68 ◽  
Author(s):  
ER Grumayer ◽  
F Griesinger ◽  
DS Hummell ◽  
RD Brunning ◽  
JH Kersey
Keyword(s):  
Bone Marrow ◽  
Cell Sorting ◽  
B Cell Development ◽  
Multiparameter Flow Cytometry ◽  
Fetal Bone ◽  
Lymphoid Development ◽  
Alternate Pathway ◽  
Lineage Markers ◽  
B Lineage

Abstract In the present study we used multiparameter flow cytometry and cell sorting to evaluate fetal bone marrow, a rich source of cells early in lymphoid development. We found CD7 to be expressed on a subset of CD19+ cells, including some that had matured to cytoplasmic mu+ (pre-B) and surface mu+ (B) cells. In addition, a less mature CD7+19+ population was characterized as mu- and CD34+/-. The CD7+19+ population was clearly distinct from the mature T cells. The CD7+19+ cells were negative for nuclear TdT in contrast to CD7–19+ cells, which frequently contained TdT. CD10, which is coexpressed on the cell surface of more than 90% of CD19+ lymphocytes, was detected in a minority of CD7+19+ lymphocytes. The CD7+19+34+ cell population may be B-lineage committed, or may represent uncommitted lymphoid precursors. The biologic role of the expression of CD7 on immature and mature cells, including those of the B lineage, may indicate (1) the presence of CD7+19+ lymphoid precursor cells and/or (2) an alternate pathway of B-cell development, in which cells coexpress CD7 with other B-lineage markers.

Differential effects of Wnt signaling in adult and fetal bone marrow-derived MSCs

Cytotherapy ◽  
2015 ◽  
Vol 17 (6) ◽  
pp. S34
Author(s):  
Maja M. Paciejweska ◽  
Marijke W. Maijenburg ◽  
Christian gilissen ◽  
Marion Kleijer ◽  
Kees Weijer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Wnt Signaling ◽  
Differential Effects ◽  
Fetal Bone

scholarly journals Molecular Modulation of Fetal Liver Hematopoietic Stem Cell Mobilization into Fetal Bone Marrow in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Huihong Zeng ◽  
Jiaoqi Cheng ◽  
Ying Fan ◽  
Yingying Luan ◽  
Juan Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Vascular Endothelial Cells ◽  
Fetal Liver ◽  
Bone Marrow Niche ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Fetal Bone

Development of hematopoietic stem cells is a complex process, which has been extensively investigated. Hematopoietic stem cells (HSCs) in mouse fetal liver are highly expanded to prepare for mobilization of HSCs into the fetal bone marrow. It is not completely known how the fetal liver niche regulates HSC expansion without loss of self-renewal ability. We reviewed current progress about the effects of fetal liver niche, chemokine, cytokine, and signaling pathways on HSC self-renewal, proliferation, and expansion. We discussed the molecular regulations of fetal HSC expansion in mouse and zebrafish. It is also unknown how HSCs from the fetal liver mobilize, circulate, and reside into the fetal bone marrow niche. We reviewed how extrinsic and intrinsic factors regulate mobilization of fetal liver HSCs into the fetal bone marrow, which provides tools to improve HSC engraftment efficiency during HSC transplantation. Understanding the regulation of fetal liver HSC mobilization into the fetal bone marrow will help us to design proper clinical therapeutic protocol for disease treatment like leukemia during pregnancy. We prospect that fetal cells, including hepatocytes and endothelial and hematopoietic cells, might regulate fetal liver HSC expansion. Components from vascular endothelial cells and bones might also modulate the lodging of fetal liver HSCs into the bone marrow. The current review holds great potential to deeply understand the molecular regulations of HSCs in the fetal liver and bone marrow in mammals, which will be helpful to efficiently expand HSCs in vitro.

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