ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors
All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the correspondin...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Becker, Amy M. [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
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| Umfang: |
480 |
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| Übergeordnetes Werk: |
Enthalten in: Interfacing 2D M - Rawat, Ashima ELSEVIER, 2021, official publication of the International Society for Experimental Hematology, Amsterdam [u.a] |
|---|---|
| Übergeordnetes Werk: |
volume:43 ; year:2015 ; number:1 ; pages:44-523 ; extent:480 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.exphem.2014.10.001 |
|---|
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| 520 | |a All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. | ||
| 520 | |a All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. | ||
| 700 | 1 | |a Walcheck, Bruce |4 oth | |
| 700 | 1 | |a Bhattacharya, Deepta |4 oth | |
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10.1016/j.exphem.2014.10.001 doi GBVA2015010000016.pica (DE-627)ELV034546758 (ELSEVIER)S0301-472X(14)00702-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Becker, Amy M. verfasserin aut ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors 2015transfer abstract 480 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. Walcheck, Bruce oth Bhattacharya, Deepta oth Enthalten in Elsevier Science Rawat, Ashima ELSEVIER Interfacing 2D M 2021 official publication of the International Society for Experimental Hematology Amsterdam [u.a] (DE-627)ELV006315852 volume:43 year:2015 number:1 pages:44-523 extent:480 https://doi.org/10.1016/j.exphem.2014.10.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 43 2015 1 44-523 480 045F 610 |
| spelling |
10.1016/j.exphem.2014.10.001 doi GBVA2015010000016.pica (DE-627)ELV034546758 (ELSEVIER)S0301-472X(14)00702-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Becker, Amy M. verfasserin aut ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors 2015transfer abstract 480 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. Walcheck, Bruce oth Bhattacharya, Deepta oth Enthalten in Elsevier Science Rawat, Ashima ELSEVIER Interfacing 2D M 2021 official publication of the International Society for Experimental Hematology Amsterdam [u.a] (DE-627)ELV006315852 volume:43 year:2015 number:1 pages:44-523 extent:480 https://doi.org/10.1016/j.exphem.2014.10.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 43 2015 1 44-523 480 045F 610 |
| allfields_unstemmed |
10.1016/j.exphem.2014.10.001 doi GBVA2015010000016.pica (DE-627)ELV034546758 (ELSEVIER)S0301-472X(14)00702-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Becker, Amy M. verfasserin aut ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors 2015transfer abstract 480 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. Walcheck, Bruce oth Bhattacharya, Deepta oth Enthalten in Elsevier Science Rawat, Ashima ELSEVIER Interfacing 2D M 2021 official publication of the International Society for Experimental Hematology Amsterdam [u.a] (DE-627)ELV006315852 volume:43 year:2015 number:1 pages:44-523 extent:480 https://doi.org/10.1016/j.exphem.2014.10.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 43 2015 1 44-523 480 045F 610 |
| allfieldsGer |
10.1016/j.exphem.2014.10.001 doi GBVA2015010000016.pica (DE-627)ELV034546758 (ELSEVIER)S0301-472X(14)00702-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Becker, Amy M. verfasserin aut ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors 2015transfer abstract 480 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. Walcheck, Bruce oth Bhattacharya, Deepta oth Enthalten in Elsevier Science Rawat, Ashima ELSEVIER Interfacing 2D M 2021 official publication of the International Society for Experimental Hematology Amsterdam [u.a] (DE-627)ELV006315852 volume:43 year:2015 number:1 pages:44-523 extent:480 https://doi.org/10.1016/j.exphem.2014.10.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 43 2015 1 44-523 480 045F 610 |
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10.1016/j.exphem.2014.10.001 doi GBVA2015010000016.pica (DE-627)ELV034546758 (ELSEVIER)S0301-472X(14)00702-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Becker, Amy M. verfasserin aut ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors 2015transfer abstract 480 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. Walcheck, Bruce oth Bhattacharya, Deepta oth Enthalten in Elsevier Science Rawat, Ashima ELSEVIER Interfacing 2D M 2021 official publication of the International Society for Experimental Hematology Amsterdam [u.a] (DE-627)ELV006315852 volume:43 year:2015 number:1 pages:44-523 extent:480 https://doi.org/10.1016/j.exphem.2014.10.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 43 2015 1 44-523 480 045F 610 |
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ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors |
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All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. |
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All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. |
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All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17 --/-- ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17 --/-- ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. |
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