MIR-125A confers multi-lineage long-term repopulating stem cell activity to murine hematopoietic progenitors

2016 ◽  
Vol 44 (9) ◽  
pp. S98
Author(s):  
Edyta Wojtowicz ◽  
Peter van Veelen ◽  
Mathilde Broekhuis ◽  
Ellen Weersing ◽  
Mir Farshid Alemdehy ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Activity ◽  
Hematopoietic Progenitors ◽  
Stem Cell Activity

scholarly journals Positional information specifies the site of organ regeneration and not tissue maintenance in planarians

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Eric M Hill ◽  
Christian P Petersen
Keyword(s):  
Stem Cell ◽  
Cell Activity ◽  
Positional Information ◽  
Tissue Homeostasis ◽  
Target Site ◽  
Maintenance And Repair ◽  
Organ Regeneration ◽  
Stem Cell Activity ◽  
Factor Expression

Most animals undergo homeostatic tissue maintenance, yet those capable of robust regeneration in adulthood use mechanisms significantly overlapping with homeostasis. Here we show in planarians that modulations to body-wide patterning systems shift the target site for eye regeneration while still enabling homeostasis of eyes outside this region. The uncoupling of homeostasis and regeneration, which can occur during normal positional rescaling after axis truncation, is not due to altered injury signaling or stem cell activity, nor specific to eye tissue. Rather, pre-existing tissues, which are misaligned with patterning factor expression domains, compete with properly located organs for incorporation of migratory progenitors. These observations suggest that patterning factors determine sites of organ regeneration but do not solely determine the location of tissue homeostasis. These properties provide candidate explanations for how regeneration integrates pre-existing tissues and how regenerative abilities could be lost in evolution or development without eliminating long-term tissue maintenance and repair.

scholarly journals Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin- Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow.

1992 ◽  
Vol 175 (1) ◽  
pp. 175-184 ◽  
Author(s):  
N Uchida ◽  
I L Weissman
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Cells ◽  
Cell Activity ◽  
Hematopoietic Stem ◽  
Stem Cell Activity ◽  
Marrow Cells

Hematopoietic stem cells (HSCs) are defined in mice by three activities: they must rescue lethally irradiated mice (radioprotection), they must self-renew, and they must restore all blood cell lineages permanently. We initially demonstrated that HSCs were contained in a rare (approximately 0.05%) subset of bone marrow cells with the following surface marker profile: Thy-1.1lo Lin- Sca-1+. These cells were capable of long-term, multi-lineage reconstitution and radioprotection of lethally irradiated mice with an enrichment that mirrors their representation in bone marrow, namely, 1,000-2,000-fold. However, the experiments reported did not exclude the possibility that stem cell activity may also reside in populations that are Thy-1.1-, Sca-1-, or Lin+. In this article stem cell activity was determined by measuring: (a) radioprotection provided by sorted cells; (b) long-term, multi-lineage reconstitution of these surviving mice; and (c) long-term, multi-lineage reconstitution by donor cells when radioprotection is provided by coinjection of congenic host bone marrow cells. Here we demonstrate that HSC activity was detected in Thy-1.1+, Sca-1+, and Lin- fractions, but not Thy-1.1-, Sca-1-, or Lin+ bone marrow cells. We conclude that Thy-1.1lo Lin- Sca-1+ cells comprise the only adult C57BL/Ka-Thy-1.1 mouse bone marrow subset that contains pluripotent HSCs.

Expression of interferon-γ by stromal cells inhibits murine long-term repopulating hematopoietic stem cell activity

1999 ◽  
Vol 27 (5) ◽  
pp. 895-903 ◽  
Author(s):  
Jian-Mei Yu ◽  
Robert V.B Emmons ◽  
Yutaka Hanazono ◽  
Stephanie Sellers ◽  
Neal S Young ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stromal Cells ◽  
Cell Activity ◽  
Interferon Γ ◽  
Hematopoietic Stem ◽  
Stem Cell Activity

scholarly journals Positional information specifies the site of organ regeneration and not tissue maintenance in planarians

2018 ◽  
Author(s):  
Eric M. Hill ◽  
Christian P. Petersen
Keyword(s):  
Stem Cell ◽  
Cell Activity ◽  
Positional Information ◽  
Tissue Homeostasis ◽  
Target Site ◽  
Maintenance And Repair ◽  
Organ Regeneration ◽  
Stem Cell Activity ◽  
Factor Expression

AbstractMost animals undergo homeostatic tissue maintenance, yet those capable of robust regeneration in adulthood use mechanisms significantly overlapping with homeostasis. Here we show in planarians that modulations to body-wide patterning systems shift the target site for eye regeneration while still enabling homeostasis of eyes outside this region. The uncoupling of homeostasis and regeneration, which can occur during normal positional rescaling after axis truncation, is not due to altered injury signaling or stem cell activity, nor specific to eye tissue. Rather, pre-existing tissues, which are misaligned with patterning factor expression domains, compete with properly located organs for incorporation of migratory progenitors. These observations suggest that patterning factors determine sites of organ regeneration but do not solely determine the location of tissue homeostasis. These properties provide candidate explanations for how regeneration integrates pre-existing tissues and how regenerative abilities could be lost in evolution or development without eliminating long-term tissue maintenance and repair.One Sentence SummaryHomeostatic tissue maintenance can occur independent of precise positional information in planarians.

SCL and Its Partner E2A Are Required for Long-Term Stem Cell Activity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 860-860
Author(s):  
Julie Lacombe ◽  
Sabine Herblot ◽  
Guy Sauvageau ◽  
Trang Hoang
Keyword(s):  
Stem Cell ◽  
Gene Dosage ◽  
Cell Activity ◽  
Host Cells ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Lymphoid Lineage ◽  
Stem Cell Activity ◽  
Serial Transplantation

Abstract SCL/TAL1 is a member of the basic helix-loop-helix family of transcription factors that also includes E2A and HEB. SCL is essential at the onset of hematopoiesis and activates transcription through heterodimerization with E2A. Both genes are expressed in long-term and short-term repopulating hematopoietic stem cells (HSCs) as assessed by expression profiling. To determine whether these genes regulate lineage commitment in HSCs and possibly other HSCs functions, we proceeded to serial transplantation of E2A-deficient or SCL-impaired HSCs. All mice were on a C57Bl/6 background and transplanted donor cells were discriminated from host cells by differential expression of CD45 isoforms. Since SCL function is dosage-sensitive, we used bone marrow cells from SCL LacZ/wt mice in which one SCL allele has been invalidated. When transplanted mice were analyzed at 4 months for reconstitution in all hematopoietic organs, SCLLacZ/wt HSCs (CD45.2) showed normal repopulating capacity in competition with wild type cells (CD45.1) as expected. Strikingly, analysis at 8 months revealed that SCLLacZ/wt HSCs were markedly impaired compared to normal HSCs. The contribution of SCLLacZ/wt cells to the Kit+Sca+Lin− (KSL) and all myeloid progenitor (CMP, MEP and GMP) populations was less than 5%. This long term defect was also observed in secondary transplantation assays. Despite this near absence of HSCs and CMPs, common lymphoid progenitors (CLPs) were almost equally composed of SCLLacZ/wt and wild type cells, and the generation of B22O positive cells was expanded when SCL gene dosage was reduced. Together, our results indicate that long-term stem cell activity requires full SCL gene dosage. Furthermore, SCL operates at the branchpoint of the myeloid and lymphoid lineages to favor the myeloid lineages. Since E2A is an obligate SCL partner, we next addressed E2A function in HSCs. As E2A−/− embryos die before birth, we therefore transplanted E14.5 fetal liver cells. E2A deficiency did not affect the number of HSCs, as assessed by limiting dilution analysis. Nonetheless, serial transplantation assays revealed that HSCs from wild type littermates could be serially transplanted beyond the fourth passage while there was an early exhaustion of E2A-deficient HSCs at the third transplantation. Together, our analyses are consistent with the view that E2A is the functional partner of SCL in HSCs and that SCL/E2A does not control the size of the HSC pool but is required for long-term HSC activity. Similarly to SCL impairment, all progenitors were decreased by E2A deficiency. There were, however, two major differences. First, CLPs were severely impaired indicating that E2A activity is required for specification of the lymphoid lineages. Second, CD11b positive cells were expanded by E2A-deficiency and this was gene dosage-dependent, consistent with the view that E2A inhibits the monocyte-granulocyte lineage. Taken together, our results indicate that SCL collaborates with E2A in HSCs to maintain their long-term activities. In contrast, at the myeloid-lymphoid branchpoint, the functions of SCL and E2A are opposite: SCL favors the myeloid lineage at the expense of the lymphoid lineage, while E2A specifies the lymphoid lineage and inhibits granulocyte-macrophage differentiation.

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