Early Growth Response Factor 1 in Aging Hematopoietic Stem Cells and Leukemia

Kulkarni, Ravi S.

doi:10.3389/fcell.2022.925761

Cited by 8 publications

(3 citation statements)

References 66 publications

(73 reference statements)

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“…Analysis of DEGs revealed a reduction in Egr1, an immediate early gene and well known transcriptional target of Srf, in Srf cKO hair cells. Various studies have established Egr1 as a regulator of hematopoietic cell differentiation and maturation (Kulkarni, 2022). Ctgf which was also significantly reduced in Srf cKO hair cells, was found to be enriched in cell growth-associated GO terms.…”

Section: Discussionmentioning

confidence: 95%

Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB

Zhou

Jin

et al. 2023

Preprint

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The MRTF-SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various cell types. However, the specific contribution of MRTF-SRF in hair cells remains unknown. In this study, we showed that hair cell-specific deletion ofSrforMrtfb, but notMrtfa, leads to similar defects in the development of stereocilia dimensions and the maintenance of cuticular plate integrity. We used FACS-based hair cell RNA-seq analysis to investigate the mechanistic underpinnings of the changes observed inSrfandMrtfbmutants, respectively. Interestingly, the transcriptome analysis revealed distinct profiles of genes regulated bySrfandMrtfb, suggesting different transcriptional regulation mechanisms of actin cytoskeleton activities mediated bySrfandMrtfb. Exogenous delivery of calponin 2 using Adeno-associated virus transduction inSrfmutants partially rescued the impairments of stereocilia dimensions and the F-actin intensity of cuticular plate, suggesting the involvement ofCnn2, as anSrfdownstream target, in regulating the hair bundle morphology and cuticular plate actin cytoskeleton organization. Our study uncovers, for the first time, the unexpected differential transcriptional regulation of actin cytoskeleton mediated bySrfandMrtfbin hair cells, and also demonstrates the critical role of SRF-CNN2 in modulating actin dynamics of the stereocilia and cuticular plate, providing new insights into the molecular mechanism underlying hair cell development and maintenance.

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Section: Discussionmentioning

confidence: 95%

Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB

Zhou

Jin

et al. 2023

Preprint

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“…Others are produced in the kidney (erythropoietin; thrombopoietin) and in the liver (thrombopoietin). Of special interest is the recently described early response growth factor 1 (ERGF1), 39 which favors the commitment of the HSC to the pluripotent myeloid progenitor and may be responsible for the decreased production of lymphocytes and increased production of granulocytes in the aged population.…”

Section: Cancer Chemotherapy and Agementioning

confidence: 99%

Cell cycle arrest: A breakthrough in the supportive care of older cancer patients

Falandry

List

Balducci

2023

J American Geriatrics Society

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Background Age is a major risk factor for the acute and chronic complications of cancer chemotherapy. The current approach to the prevention of these complications is reactive and involves the reduction of the doses and the delay of treatment which may compromise the outcome. There is a limited number of antidotes to chemotherapy toxicity and these have complications of their own. Oldest old and frail patients are mostly excluded from life saving cancer treatment due to the risk of severe and even lethal complications. Methods molecular biology has revealed that different checkpoints control the proliferative cycle of normal and neoplastic cells. Two new drugs, Trilaciclib and ALRN‐6924 may cause a temporary cell cycle arrest (CCA) of normal cells without blocking the proliferation of the neoplastic ones and render the normal cells temporarily invulnerable to the toxicity of chemotherapy. We reviewed the publications related to these drugs on the Medline, the published drug information and the presentations to major medical conferences. Results In three randomized controlled phase II trials Trilaciclib proved effective in preventing neutropenia, thrombocytopenia and anemia in patients with non small cell lung cancer with non proficient RB1 gene. Forty‐five percent of patients were 65 and older and age did not prevent the effectiveness of the drug. Trilaciclib was approved by the FDA for the management of these patients. ALRN‐6924 appeared promising in preventing myelotoxicity in patients whose cancer had deleted or mutated TP53, but failed to show any significant activity in a randomized controlled study. The development of this drug is now on hold Conclusions CCA is a novel proactive approach to the toxicity of chemotherapy of special interest to older patients. At the very least it may prevent all forms of myelotoxicity with a single agent, obviating the risk and cost of polypharmacy. It allows to avoid the complications of myelopoietic growth factors which include severe pain, stem cell competition, bone marrow exhaustion, and hematological malignancies. It may allow the treatment of frail patients with full chemotherapy doses. It is also reasonable to expect that may complications other common and sometimes lethal complications of chemotherapy such as stomatitis, esophagitis, diarrhea and dehydration.

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“…In cell cycle regulation, the transcription factors play a central role by monitoring the cell cycle progression. Early growth response 1 (Egr1) is an essential transcription factor in the maintenance of HSC number and their retention in the BM (Kulkarni, 2022). Min et al (2008) performed Egr1 knockout studies in mice to understand its role in normal hematopoiesis.…”

Section: Regulation Of Normal and Dysregulated Hematopoiesis Via Cell...mentioning

confidence: 99%

A comprehensive analysis of cell‐autonomous and non‐cell‐autonomous regulation of myeloid leukemic cells: The prospect of developing novel niche‐targeting therapies

Pendse

Chavan

Kale

et al. 2023

Cell Biology International

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Leukemic cells (LCs) arise from the hematopoietic stem/and progenitor cells (HSCs/HSPCs) and utilize cues from the bone marrow microenvironment (BMM) for their regulation in the same way as their normal HSC counterparts. Mesenchymal stromal cells (MSCs), a vital component of the BMM promote leukemogenesis by creating a protective and immune‐tolerant microenvironment that can support the survival of LCs, helping them escape chemotherapy, thereby resulting in the relapse of leukemia. Conversely, MSCs also induce apoptosis in the LCs and inhibit their proliferation by interfering with their self‐renewal potential. This review discusses the work done so far on cell‐autonomous (intrinsic) and MSCs‐mediated non‐cell‐autonomous (extrinsic) regulation of myeloid leukemia with a special focus on the need to investigate the extrinsic regulation of myeloid leukemia to understand the contrasting role of MSCs in leukemogenesis. These mechanisms could be exploited to formulate novel therapeutic strategies that specifically target the leukemic microenvironment.

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Early Growth Response Factor 1 in Aging Hematopoietic Stem Cells and Leukemia

Cited by 8 publications

References 66 publications

Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB

Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB

Cell cycle arrest: A breakthrough in the supportive care of older cancer patients

A comprehensive analysis of cell‐autonomous and non‐cell‐autonomous regulation of myeloid leukemic cells: The prospect of developing novel niche‐targeting therapies

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