TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC

Ying Liu, Khalid A. Timani, Charlie Mantel, Yan Fan, Giao Hangoc, Scott Cooper, Johnny Jianglin He, Hal E. Broxmeyer

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Intracellular factors are involved in and essential for hematopoiesis. HIV-1 Tat-interacting protein of 110 kDa (TIP110; p110nrb/SART3/p110) is an RNA-binding nuclear protein implicated in the regulation of HIV-1 gene and host gene transcription, pre-mRNA splicing, and cancer immunology. In the present study, we demonstrate a role for TIP110 in the regulation of hematopoiesis. TIP110 was expressed in human CD34+ cells and decreased with differentiation of CD34+ cells. TIP110 mRNA was also expressed in phenotyped mouse marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Using TIP110 transgenic (TIP110 TG) and haploinsufficient (TIP110+/-) mice, we found that increased TIP110 expression enhanced HPC numbers, survival, and cell cycling, whereas decreased TIP110 expression had the opposite effects. Moreover, TIP110+/- bone marrow HPCs responded more effectively, and TIP110TG HPCs less effectively, than those of wild-type control mice to recovery from the cell-cycle-active drug 5-fluorouracil (5-FU). Unexplained sex differences were noted in HSC competitive repopulating ability, but not HPC numbers, in TIP110TG mice. Intracellularly, TIP110 regulated CMYC and GATA2 expression at the transcriptional level, and TIP110 and CMYC reciprocally regulated the expression of each other. These results demonstrate a role for TIP110 in the regulation of hematopoiesis, effects that are likely linked to TIP110 regulation of CMYC.

Original languageEnglish
Pages (from-to)5643-5651
Number of pages9
JournalBlood
Volume117
Issue number21
DOIs
StatePublished - 26 May 2011

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Hematopoiesis
Hematopoietic Stem Cells
Stem cells
Genes
Cells
Immunology
RNA Precursors
Transcription
Nuclear Proteins
Fluorouracil
Bone
RNA
Recovery
Messenger RNA
HIV-1
Pharmaceutical Preparations
Cell Count
Bone Marrow
Proteins
tat Gene Products

Cite this

Liu, Y., Timani, K. A., Mantel, C., Fan, Y., Hangoc, G., Cooper, S., ... Broxmeyer, H. E. (2011). TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC. Blood, 117(21), 5643-5651. https://doi.org/10.1182/blood-2010-12-325332
Liu, Ying ; Timani, Khalid A. ; Mantel, Charlie ; Fan, Yan ; Hangoc, Giao ; Cooper, Scott ; He, Johnny Jianglin ; Broxmeyer, Hal E. / TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC. In: Blood. 2011 ; Vol. 117, No. 21. pp. 5643-5651.
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title = "TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC",
abstract = "Intracellular factors are involved in and essential for hematopoiesis. HIV-1 Tat-interacting protein of 110 kDa (TIP110; p110nrb/SART3/p110) is an RNA-binding nuclear protein implicated in the regulation of HIV-1 gene and host gene transcription, pre-mRNA splicing, and cancer immunology. In the present study, we demonstrate a role for TIP110 in the regulation of hematopoiesis. TIP110 was expressed in human CD34+ cells and decreased with differentiation of CD34+ cells. TIP110 mRNA was also expressed in phenotyped mouse marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Using TIP110 transgenic (TIP110 TG) and haploinsufficient (TIP110+/-) mice, we found that increased TIP110 expression enhanced HPC numbers, survival, and cell cycling, whereas decreased TIP110 expression had the opposite effects. Moreover, TIP110+/- bone marrow HPCs responded more effectively, and TIP110TG HPCs less effectively, than those of wild-type control mice to recovery from the cell-cycle-active drug 5-fluorouracil (5-FU). Unexplained sex differences were noted in HSC competitive repopulating ability, but not HPC numbers, in TIP110TG mice. Intracellularly, TIP110 regulated CMYC and GATA2 expression at the transcriptional level, and TIP110 and CMYC reciprocally regulated the expression of each other. These results demonstrate a role for TIP110 in the regulation of hematopoiesis, effects that are likely linked to TIP110 regulation of CMYC.",
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Liu, Y, Timani, KA, Mantel, C, Fan, Y, Hangoc, G, Cooper, S, He, JJ & Broxmeyer, HE 2011, 'TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC', Blood, vol. 117, no. 21, pp. 5643-5651. https://doi.org/10.1182/blood-2010-12-325332

TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC. / Liu, Ying; Timani, Khalid A.; Mantel, Charlie; Fan, Yan; Hangoc, Giao; Cooper, Scott; He, Johnny Jianglin; Broxmeyer, Hal E.

In: Blood, Vol. 117, No. 21, 26.05.2011, p. 5643-5651.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC

AU - Liu, Ying

AU - Timani, Khalid A.

AU - Mantel, Charlie

AU - Fan, Yan

AU - Hangoc, Giao

AU - Cooper, Scott

AU - He, Johnny Jianglin

AU - Broxmeyer, Hal E.

PY - 2011/5/26

Y1 - 2011/5/26

N2 - Intracellular factors are involved in and essential for hematopoiesis. HIV-1 Tat-interacting protein of 110 kDa (TIP110; p110nrb/SART3/p110) is an RNA-binding nuclear protein implicated in the regulation of HIV-1 gene and host gene transcription, pre-mRNA splicing, and cancer immunology. In the present study, we demonstrate a role for TIP110 in the regulation of hematopoiesis. TIP110 was expressed in human CD34+ cells and decreased with differentiation of CD34+ cells. TIP110 mRNA was also expressed in phenotyped mouse marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Using TIP110 transgenic (TIP110 TG) and haploinsufficient (TIP110+/-) mice, we found that increased TIP110 expression enhanced HPC numbers, survival, and cell cycling, whereas decreased TIP110 expression had the opposite effects. Moreover, TIP110+/- bone marrow HPCs responded more effectively, and TIP110TG HPCs less effectively, than those of wild-type control mice to recovery from the cell-cycle-active drug 5-fluorouracil (5-FU). Unexplained sex differences were noted in HSC competitive repopulating ability, but not HPC numbers, in TIP110TG mice. Intracellularly, TIP110 regulated CMYC and GATA2 expression at the transcriptional level, and TIP110 and CMYC reciprocally regulated the expression of each other. These results demonstrate a role for TIP110 in the regulation of hematopoiesis, effects that are likely linked to TIP110 regulation of CMYC.

AB - Intracellular factors are involved in and essential for hematopoiesis. HIV-1 Tat-interacting protein of 110 kDa (TIP110; p110nrb/SART3/p110) is an RNA-binding nuclear protein implicated in the regulation of HIV-1 gene and host gene transcription, pre-mRNA splicing, and cancer immunology. In the present study, we demonstrate a role for TIP110 in the regulation of hematopoiesis. TIP110 was expressed in human CD34+ cells and decreased with differentiation of CD34+ cells. TIP110 mRNA was also expressed in phenotyped mouse marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Using TIP110 transgenic (TIP110 TG) and haploinsufficient (TIP110+/-) mice, we found that increased TIP110 expression enhanced HPC numbers, survival, and cell cycling, whereas decreased TIP110 expression had the opposite effects. Moreover, TIP110+/- bone marrow HPCs responded more effectively, and TIP110TG HPCs less effectively, than those of wild-type control mice to recovery from the cell-cycle-active drug 5-fluorouracil (5-FU). Unexplained sex differences were noted in HSC competitive repopulating ability, but not HPC numbers, in TIP110TG mice. Intracellularly, TIP110 regulated CMYC and GATA2 expression at the transcriptional level, and TIP110 and CMYC reciprocally regulated the expression of each other. These results demonstrate a role for TIP110 in the regulation of hematopoiesis, effects that are likely linked to TIP110 regulation of CMYC.

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U2 - 10.1182/blood-2010-12-325332

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