Faculty Opinions recommendation of Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5-deficient pre-B I-cell clones.

Author(s):  
Ana Cumano
Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3604-3604
Author(s):  
Jens M. Nygren ◽  
Simon Stott ◽  
Karina Liuba ◽  
Martin Breitbach ◽  
Willhelm Röll ◽  
...  

Abstract Several recent studies have suggested that bone marrow (BM) cells can contribute to non-hematopoietic cell lineages through cell fusion rather than transdiffentiation. As this phenomenon has been observed in multiple organs, including the brain and heart, without prior infliction of organ-specific insults, it has been proposed that BM cells might contribute to replacement of non-hematopoietic cell lineages during steady state, and that BM transplantation might be developed as a therapeutic modality in diseases of these organs. However, as all observations of BM-derived cell fusion in vivo have been made in lethally irradiated mice reconstituted with genetically marked BM cells, we addressed to what degree cell fusion occurs normally and/or in response to whole body irradiation. To be able to distinguish between these possibilities we used c-kit deficient (w41/w41) mice, which unlike wild type mice do not require irradiation-induced myeloablation to facilitate reconstitution of transplanted BM cells. Noteworthy, no BM-derived cell fusion events were observed in the brain (purkinje neurons) or heart (cardiomyocytes) when unconditioned w41/w41 mice were reconstituted with beta actin GFP transgenic BM cells. In striking contrast, following whole body irradiation (875 rad), BM-derived cell fusion was observed in recipient cardiomyocytes and purkinje neurons of all BM transplanted mice. Thus, spontaneous adult BM-derived cell fusion does not occur in steady state but is potently facilitated by irradiation-induced injuries to the organs in which cell fusion occurs.


2021 ◽  
Author(s):  
Bingqiang Wen ◽  
Guolun Wang ◽  
Enhong Li ◽  
Olena A. Kolesnichenko ◽  
Zhaowei Tu ◽  
...  

Generation of bone marrow (BM) from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) promises to accelerate the development of future cell therapies for life-threatening disorders. However, such approach is limited by technical challenges to produce a mixture of functional BM progenitor cells able to replace all hematopoietic cell lineages. Herein, we used blastocyst complementation to simultaneously produce all BM hematopoietic cell lineages from mouse ESCs in a rat. Based on FACS analysis and single-cell RNA sequencing, mouse ESCs differentiated into hematopoietic progenitor cells and multiple hematopoietic cell types that were indistinguishable from normal mouse BM cells based on gene expression signatures and cell surface markers. Transplantation of ESC-derived BM cells from mouse-rat chimeras rescued lethally-irradiated syngeneic mice and resulted in long-term contribution of donor cells to hematopoietic cell lineages. Altogether, a fully functional bone marrow was generated from mouse ESCs using rat embryos as “bioreactors”.


Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 472-478 ◽  
Author(s):  
Christoph Schaniel ◽  
Ludovica Bruno ◽  
Fritz Melchers ◽  
Antonius G. Rolink

Abstract Pax5-deficient pre-B I–cell clones, transplanted into natural killer (NK)–cell–deficient RAG2−/−IL-2Rγ−/−hosts, populate the NK-cell compartment with functional NK cells. NK-cell generation fromPax5−/−pre-B I cells is also observed in NK-cell–proficient Balb/c RAG2−/− hosts. In the same Balb/c RAG2−/− hosts,Pax5−/− pre-B I–cell clones not only populate the pre-B I–cell compartment and fill the deficient T-cell–lineage compartment in the thymus and the periphery of all hosts, as shown before, they also generate CD8α− and CD8α+ dendritic cells (DCs), macrophages, and granulocytes in vivo in approximately half the hosts. In some recipients, practically all the mature myeloid cells are ofPax5−/− origin, indicating the effectiveness by which Pax5−/−pre-B I cells can compete with endogenous myeloid precursors. In a smaller percentage of hosts, the generation of Pax5−/−pre-B I–cell–derived erythrocytes is observed 4 to 6 months after transplantation. The results indicate that Pax5−/−pre-B I cells can develop in vivo in hosts that have undergone transplantation to erythroid, myeloid, and lymphoid cell lineages. Hence, the Pax5−/−mutation introduces an unusual instability of differentiation in pre-B I cells so that they appear to dedifferentiate as far back as the pluripotent hematopoietic stem cell.


2020 ◽  
Vol 7 (2) ◽  
pp. 36 ◽  
Author(s):  
João P. Cotovio ◽  
Tiago G. Fernandes

Liver disease is one of the leading causes of death worldwide, leading to the death of approximately 2 million people per year. Current therapies include orthotopic liver transplantation, however, donor organ shortage remains a great challenge. In addition, the development of novel therapeutics has been limited due to the lack of in vitro models that mimic in vivo liver physiology. Accordingly, hepatic cell lineages derived from human pluripotent stem cells (hPSCs) represent a promising cell source for liver cell therapy, disease modelling, and drug discovery. Moreover, the development of new culture systems bringing together the multiple liver-specific hepatic cell types triggered the development of hPSC-derived liver organoids. Therefore, these human liver-based platforms hold great potential for clinical applications. In this review, the production of the different hepatic cell lineages from hPSCs, including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids will be assessed, while current biomedical applications will be highlighted.


1970 ◽  
Vol 131 (6) ◽  
pp. 1261-1270 ◽  
Author(s):  
George C. Saunders ◽  
Douglas Swartzendruber

Cells capable of reacting with sheep erythrocyte (SRBC) antigen to maturate and produce hemolysin appear simultaneously in the bone marrow and spleen of 1-day old Swiss-Webster mice. However, hemolysin-producing cell clones (HPCC) do not result. Complete functional precursor units generally appear in the spleens of mice older than 3 days. In vivo and in vitro data correlate well in this regard. Complete precursor units are not seen in the bone marrow and only very rarely in the thymus. The efficiency of precursor units of neonatal mice when they become functional approximates that of the mature animal when based on the doubling time of plaque-forming cells (PFC). Possible explanations of the initial appearance of incomplete precursor units have been discussed.


2005 ◽  
Vol 115 (3) ◽  
pp. 313-322 ◽  
Author(s):  
L AUSUBEL ◽  
K OCONNOR ◽  
C BAECHERALLEN ◽  
C TROLLMO ◽  
B KESSLER ◽  
...  

2009 ◽  
Vol 206 (13) ◽  
pp. 2907-2914 ◽  
Author(s):  
Tanja A. Schwickert ◽  
Boris Alabyev ◽  
Tim Manser ◽  
Michel C. Nussenzweig

Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude that GCs are dynamic anatomical structures that can be reutilized by newly activated B cells during immune responses.


2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Christine V. Ichim ◽  
Dzana D. Dervovic ◽  
Lap Shu Alan Chan ◽  
Claire J. Robertson ◽  
Alden Chesney ◽  
...  

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1240-1243
Author(s):  
M Keinanen ◽  
S Knuutila ◽  
CD Bloomfield ◽  
E Elonen ◽  
A de la Chapelle

To determine the hematopoietic cell lineage of mitotic cells in human bone marrow on direct examination and after 24-hour culture, marrow mitoses from four healthy individuals were studied, using a new technique that allows analysis of karyotypes in cells whose cell membrane and cytoplasm have been preserved. Mitoses were identified as being of erythroid lineage by immunofluorescent staining for surface glycophorin A and as being of granulocytic lineage by cytoplasmic staining for Sudan black B. On direct marrow examination without prior culture, the great majority of mitoses (74% to 90%) were of erythroid lineage; only a few (0% to 10%) were granulocytic. After 24-hour culture, the percentage of erythroid mitoses (15% to 40%) decreased, while the percentage of granulocytic mitoses (58% to 87%) increased strikingly. These data indicate that mitotic cells of different hematopoietic cell lineages predominate in marrow at different culture times and offer a plausible explanation for the high frequency of normal karyotypes in acute myeloid leukemia after direct marrow cytogenetic evaluation.


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