In vitro production of erythropoietin by mouse fetal liver

Zucali, JR; Stevens, V; Mirand, E. A.

doi:10.1182/blood.v46.1.85.bloodjournal46185

Cited by 3 publications

(3 citation statements)

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“…Although in CK2β KO more mature erythroid cells (Ter119 + ) we did not detect a depletion in EPO‐R protein levels (Figure 5D), the trend of reduction in EPO concentration could suggest a less effective stimulation upstream of this receptor (Figure 5C). Since during fetal life EPO is mainly produced by hepatocytes and macrophages of the blood islands, 84 we cannot exclude that macrophage production of EPO is impaired in CK2β KO embryos. Moreover, we observed in KO embryos the down‐modulation of Siglec1 , Vacam1, and Selplg (Figure 5A) encoding for the adhesion molecules essential for the blood island formation 61 .…”

Section: Discussionmentioning

confidence: 99%

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis

Quotti Tubi,

Canovas Nunes,

Mandato

et al. 2023

HemaSphere

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The Ser-Thr kinase CK2 plays important roles in sustaining cell survival and resistance to stress and these functions are exploited by different types of blood tumors. Yet, the physiological involvement of CK2 in normal blood cell development is poorly known. Here, we discovered that the β regulatory subunit of CK2 is critical for normal hematopoiesis in the mouse. Fetal livers of conditional CK2β knockout embryos showed increased numbers of hematopoietic stem cells associated to a higher proliferation rate compared to control animals. Both hematopoietic stem and progenitor cells (HSPCs) displayed alterations in the expression of transcription factors involved in cell quiescence, self-renewal, and lineage commitment. HSPCs lacking CK2β were functionally impaired in supporting both in vitro and in vivo hematopoiesis as demonstrated by transplantation assays. Furthermore, KO mice developed anemia due to a reduced number of mature erythroid cells. This compartment was characterized by dysplasia, proliferative defects at early precursor stage, and apoptosis at late-stage erythroblasts. Erythroid cells exhibited a marked compromise of signaling cascades downstream of the cKit and erythropoietin receptor, with a defective activation of ERK/JNK, JAK/STAT5, and PI3K/AKT pathways and perturbations of several transcriptional programs as demonstrated by RNA-Seq analysis. Moreover, we unraveled an unforeseen molecular mechanism whereby CK2 sustains GATA1 stability and transcriptional proficiency. Thus, our work demonstrates new and crucial functions of CK2 in HSPC biology and in erythropoiesis.

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Section: Discussionmentioning

confidence: 99%

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis

Quotti Tubi,

Canovas Nunes,

Mandato

et al. 2023

HemaSphere

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“…Epo is produced in the murine fetal liver ( Jacobs et al , 1985 ; Koury et al , 1991 ). Since unfractionated liver cells were cultured for this study, it is possible that the Epo‐independent CFU‐E growth and the SCF‐dependent BFU‐E growth described here were mediated by Epo released in the culture by the accessory cells ( Zucali et al , 1975 ). This possibility was excluded, at least for SCF, by comparing its effects on the proliferation and differentiation of progenitors cells purified from FL and AM (CFU‐E are not enriched by the purification strategy used in this study; Migliaccio et al , 1988 ).…”

Section: Discussionmentioning

confidence: 99%

Stem cell factor induces proliferation and differentiation of fetal progenitor cells in the mouse

et al. 1998

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Summary.We have investigated the kinetics of the amplification of the progenitor cell compartments (CFC) in haemopoietic organs during murine ontogenesis and compared the growth requirements of fetal and adult CFC. Two haemopoietic phases were recognized in the fetal liver (FL): an exponential growth phase, from 11·5 to 15·5 d post conception (p.c.), during which the mean number of nucleated cells and of CFC in the FL increased from 4·9 × 10 5 to 7·0 × 10 7 and from 4·5 × 10 3 to 2·7 × 10 5 , respectively, and a recessive phase after 15·5 d p.c., during which the CFC number in the FL gradually decreased, although some CFC were still detectable in the liver after birth. In serum-deprived cultures, FL and adult marrow (AM) CFC had similar responses to GM-CSF, and did not respond to G-CSF or IL-3. In contrast, FL, but not AM, erythroid colonies grew Epo-independently whereas SCF alone induced formation of maximal numbers of erythroid bursts from FL, but not from AM cells. The proliferative and differentiative effect of SCF alone on fetal cells was confirmed in serum-deprived cultures of purified early progenitor cells isolated by cell sorting on the basis of multiple parameters from FL and AM light-density cells. In culture of purified FL cells, SCF alone induced a similar amplification of total cells (maximal amplification at day 12: 800-300-fold) and total CFC (11-38-fold of maximal amplification at day 6) to the combination of SCF plus IL-3 (1300-800-fold amplification of total cells and 31-88-fold amplification of CFC). In contrast, SCF alone allowed only survival of purified AM early progenitor cells. Therefore FL early progenitor cells have an intrinsic higher potential than their adult counterpart to respond to SCF, confirming the potent role of this growth factor in the development of the murine haemopoietic system.

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“…Erythropoietin has been reported to enhance the synthesis of DNA (Paul & Hunter, 1969) and RNA (Djaldetti et al, 1972) in erythroid cells of foetal mouse liver, and these cells produce erythropoietin in vitro (Zucali et al, 1975). It would be interesting to study the effects oferythropoietin on folate-dependent enzymes such as thymidylate synthetase, to test whether the effect of the hormone on erythropoietic cell division is mediated by the activity of these enzymes.…”

Section: Methodsmentioning

confidence: 99%