scholarly journals Permanent loss in stem cell self renewal capacity following stress to the marrow

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1193-1196 ◽  
Author(s):  
P Mauch ◽  
M Rosenblatt ◽  
S Hellman
Keyword(s):  
Stem Cell ◽  
Hind Limb ◽  
Cell Function ◽  
Cell Compartment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Permanent Loss ◽  
Marrow Cellularity ◽  
Stem Cell Pool

A technique of irradiating the entire mouse except for one hind limb was developed to provide repeated proliferative demand on the stem cell pool. Animals received 200 cGY weekly for a total dose of 3,400 to 4,000 cGy. During irradiation, shielded bone marrow cellularity was similar to that of unirradiated controls. Shielded marrow colony- forming unit (CFUs) content increased while marrow CFUs self renewal capacity decreased as compared with unirradiated age-matched controls. Following irradiation experimental animals were monitored monthly for 10 to 12 months for marrow cellularity, CFUs content, and self renewal capacity. Shielded marrow cellularity and CFUs content remained elevated over age-matched controls throughout the period of observation. These findings are compatible with the requirement of the shielded hind limb to provide hematopoietic support for the remainder of the animal. Shielded marrow self renewal capacity, a measurement reflecting primitive hematopoietic stem cell function, remained depressed and did not recover with time. These experiments provide evidence for there being limitations on the self renewal capacity of the stem cell compartment. While the small amount of shielded marrow had sufficient capacity to support the animal its average self renewal capacity was permanently reduced.

scholarly journals Permanent loss in stem cell self renewal capacity following stress to the marrow

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1193-1196 ◽  
Author(s):  
P Mauch ◽  
M Rosenblatt ◽  
S Hellman
Keyword(s):  
Stem Cell ◽  
Hind Limb ◽  
Cell Function ◽  
Cell Compartment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Permanent Loss ◽  
Marrow Cellularity ◽  
Stem Cell Pool

Abstract A technique of irradiating the entire mouse except for one hind limb was developed to provide repeated proliferative demand on the stem cell pool. Animals received 200 cGY weekly for a total dose of 3,400 to 4,000 cGy. During irradiation, shielded bone marrow cellularity was similar to that of unirradiated controls. Shielded marrow colony- forming unit (CFUs) content increased while marrow CFUs self renewal capacity decreased as compared with unirradiated age-matched controls. Following irradiation experimental animals were monitored monthly for 10 to 12 months for marrow cellularity, CFUs content, and self renewal capacity. Shielded marrow cellularity and CFUs content remained elevated over age-matched controls throughout the period of observation. These findings are compatible with the requirement of the shielded hind limb to provide hematopoietic support for the remainder of the animal. Shielded marrow self renewal capacity, a measurement reflecting primitive hematopoietic stem cell function, remained depressed and did not recover with time. These experiments provide evidence for there being limitations on the self renewal capacity of the stem cell compartment. While the small amount of shielded marrow had sufficient capacity to support the animal its average self renewal capacity was permanently reduced.

scholarly journals Effects of Radiation on The Capacity of The Stem Cell Compartment to Differentiate into Granulocytic and Erythrocytic Progeny

Blood ◽  
1969 ◽  
Vol 34 (2) ◽  
pp. 141-156 ◽  
Author(s):  
SAMUEL HELLMAN ◽  
HELEN E. GRATE ◽  
JOHN T. CHAFFEY
Keyword(s):  
Stem Cell ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Cell Counts ◽  
Stem Cell Compartment ◽  
Cell Pool ◽  
White Blood Cell Counts ◽  
Effects Of Radiation ◽  
Stem Cell Pool

Abstract Different methods have been used to measure the survival following radiation of the hematopoietic stem cell pool. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both methods, irradiated recipient mice receive syngeneic bone marrow. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly-formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. This latter is a granulocyte response and has been shown to be a measure of the marrow granulocyte reserve. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive initially than as measured by its ability to produce granulocytic progeny. Erythropoietic repopulating ability begins recovery more promptly than the granulopoietic. These effects appear to be due to the host milieu rather than any direct effect of radiation on the stem cells, resulting in initial conservation of granulopoiesis relative to erythropoiesis with subsequent compensatory recovery of erythropoiesis. Because of recent evidence suggesting a common stem cell, these results are interpreted as consistent with the notion that radiation affects not only stem cell proliferation, but also the direction and extent of differentiation.

scholarly journals PR-domain–containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3853-3861 ◽  
Author(s):  
Yi Zhang ◽  
Sandra Stehling-Sun ◽  
Kimberly Lezon-Geyda ◽  
Subhash C. Juneja ◽  
Lucie Coillard ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Critical Role ◽  
Growth Control ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Pr Domain

Abstract The Mds1 and Evi1 complex locus (Mecom) gives rise to several alternative transcripts implicated in leukemogenesis. However, the contribution that Mecom-derived gene products make to normal hematopoiesis remains largely unexplored. To investigate the role of the upstream transcription start site of Mecom in adult hematopoiesis, we created a mouse model with a lacZ knock-in at this site, termed MEm1, which eliminates Mds1-Evi1 (ME), the longer, PR-domain–containing isoform produced by the gene (also known as PRDM3). β-galactosidase–marking studies revealed that, within hematopoietic cells, ME is exclusively expressed in the stem cell compartment. ME deficiency leads to a reduction in the number of HSCs and a complete loss of long-term repopulation capacity, whereas the stem cell compartment is shifted from quiescence to active cycling. Genetic exploration of the relative roles of endogenous ME and EVI1 isoforms revealed that ME preferentially rescues long-term HSC defects. RNA-seq analysis in Lin−Sca-1+c-Kit+ cells (LSKs) of MEm1 documents near complete silencing of Cdkn1c, encoding negative cell-cycle regulator p57-Kip2. Reintroduction of ME into MEm1 LSKs leads to normalization of both p57-Kip2 expression and growth control. Our results clearly demonstrate a critical role of PR-domain–containing ME in linking p57-kip2 regulation to long-term HSC function.

scholarly journals Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment

2021 ◽  
Vol 539 ◽  
pp. 34-41
Author(s):  
Taro Sakamaki ◽  
Kevin S. Kao ◽  
Katsuyuki Nishi ◽  
James Y. Chen ◽  
Kay Sadaoka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Compartment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment

Genetic control of hematopoietic stem cell frequency in mice is mostly cell autonomous

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2446-2448 ◽  
Author(s):  
Christa E. Müller-Sieburg ◽  
Rebecca H. Cho ◽  
Hans B. Sieburg ◽  
Sergey Kupriyanov ◽  
Roy Riblet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Compartment ◽  
Cell Frequency ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Cell Pool ◽  
The Difference ◽  
Extrinsic Effects ◽  
Stem Cell Pool

Abstract Previously we reported that the size of the stem cell compartment (measured as LTC-IC) is 11-fold greater in DBA/2 than in C57BL/6 mice, and we identified genes that regulate the size of the stem cell pool. To determine whether stem cell intrinsic or extrinsic events account for these differences, we created chimeras by aggregating morulae from the strains C57BL/6 and DBA/2. In these chimeras stem cells of both genotypes are exposed to a common mixed environment. Thus, an equalization of stem cell frequencies is expected if stem cell extrinsic effects dominate. Conversely, the parental ratio of LTC-IC should be preserved if the regulation is stem cell autonomous. For each chimera, individual LTC-IC were genotyped on the clonal levels by analyzing their progeny. We found that most of the difference that regulates the size of the stem cell compartment was intrinsic.

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